Macrolitter budget and spatial distribution in a groyne field along the Waal river.

Current research on riverine macrolitter does not yet provide a theoretic framework on the dynamics behind its accumulation and distribution along riverbanks. In an attempt to better understand these dynamics a detailed field survey of three months was conducted in which location of macrolitter items within a single groyne field along the Waal riverbanks was tracked. The data provided insight into the daily changing patterns of spatial item distribution with respect to the waterline. Furthermore, the rates of item uptake and deposition were monitored and related to hydrologic fluctuations. Uptake was initiated by rising water levels and was generally higher when the water level increased faster. Deposition occurred continuously, despite hydrologic fluctuations. This caused the riverbank macrolitter budget to be positive during stable or dropping water levels and negative during rising water levels. Although the results show clear patterns an extended monitoring duration is required to fully understand the fate of plastic objects.

Freshwater fish biodiversity restoration in floodplain rivers requires connectivity and habitat heterogeneity at multiple spatial scales.

With a sixth mass extinction looming and freshwater biodiversity declining at unprecedented rates, evaluating ecological efficacy of river restoration efforts is critical in combatting global biodiversity loss. Here, we present a comprehensive study of the functioning for fishes of 46 river restoration projects in the river Rhine, one of the world's most heavily engineered lowland rivers. Floodplains with permanent, either one- or two-sided lateral connectivity to the main channel, favour total fish abundance, and are essential as nursery areas for riverine fishes. Habitat heterogeneity had a strong positive effect on species richness but was negatively related with fish abundances. However, the effects of environmental variables varied between ecological groups and spatial scales. Surprisingly, richness of critical rheophilic fishes declined with large-scale habitat heterogeneity (~1000 m), while it increased at small scales (~100 m), possibly because of the presence of unfavourable habitats for this ecological group at larger scales. Clearly, there is no one-size-fits-all design for river restoration projects. Whether a river section is free-flowing or impounded dictates the scope and efficacy of restoration projects and, within a river section, multiple complementary restoration projects might be key to mitigate freshwater fish biodiversity loss. An essential element for success is that these projects should retain permanent lateral connection to the main channel.

The upgraded TOMAS device: A toroidal plasma facility for wall conditioning, plasma production, and plasma-surface interaction studies.

The Toroidal Magnetized System device has been significantly upgraded to enable development of various wall conditioning techniques, including methods based on ion and electron cyclotron (IC/EC) range of frequency plasmas, and to complement plasma-wall interaction research in tokamaks and stellarators. The toroidal magnetic field generated by 16 coils can reach its maximum of 125 mT on the toroidal axis. The EC system is operated at 2.45 GHz with up to 6 kW forward power. The IC system can couple up to 6 kW in the frequency range of 10 MHz-50 MHz. The direct current glow discharge system is based on a graphite anode with a maximum voltage of 1.5 kV and a current of 6 A. A load-lock system with a vertical manipulator allows exposure of material samples. A number of diagnostics have been installed: single- and triple-pin Langmuir probes for radial plasma profiles, a time-of-flight neutral particle analyzer capable of detecting neutrals in the energy range of 10 eV-1000 eV, and a quadrupole mass spectrometer and video systems for plasma imaging. The majority of systems and diagnostics are controlled by the Siemens SIMATIC S7 system, which also provides safety interlocks.

Longitudinal training dams mitigate effects of shipping on environmental conditions and fish density in the littoral zones of the river Rhine.

The stability of habitat conditions in littoral zones of navigated rivers is strongly affected by shipping induced waves and water displacements. In particular, the increase of variability in flow conditions diminishes the suitability of these habitats for juvenile fishes. Recently, a novel ecosystem based river management strategy has resulted in the replacement of traditional river training structures (i.e., groynes) by longitudinal training dams (LTDs), and the creation of shore channels in the river Waal, the main, free-flowing and intensively navigated distributary of the river Rhine in the Netherlands. It was hypothesized that these innovative LTDs mitigated the effects of shipping on fishes by maintaining the natural variability of habitat conditions in the littoral zones during ship passages whereby shore channels served as refugia for juvenile fishes. Measurements of abiotic conditions showed a significantly lower water level fluctuation and significantly higher flow stability in shore channels compared to groyne fields. Flow velocity did not differ, nor did the variation in flow velocity fluctuation during ship passage between these habitats. Densities of fish were found to be significantly higher in the littoral zones of shore channels compared to nearby groyne fields. Moreover, electrofishing along the inner side of the newly constructed LTD showed a significant linear relationship between fish density and distance from highly dynamic in- and outflow sections and to lowered inflow sections in the LTD. Results of our field sampling clearly indicate successful ecological rehabilitation of littoral zones that coincides with a facilitation of navigation in the main river channel and increased flood safety.

Isotope effect and multiscale physics in fusion plasmas.

The mechanism governing the impact of the mass isotope on plasma confinement is still one of the main scientific conundrums facing the magnetic fusion community after more than thirty years of intense research. We have investigated the properties of local turbulence and long-range correlations in hydrogen and deuterium plasmas in the TEXTOR tokamak. Experimental findings have shown a systematic increasing in the amplitude of long-range correlations during the transition from hydrogen to deuterium dominated plasmas. These results provide the first direct experimental evidence of the importance of multiscale physics for unraveling the physics of the isotope effect in fusion plasmas.

Development of the gas-puff imaging diagnostic in the TEXTOR tokamak.

Gas puff imaging (GPI) [S. J. Zweben, D. P. Stotler et al., Phys. Plasmas 9, 1981 (2002); R. J. Maqueda, G. A. Wurden et al., Rev. Sci. Instrum. 74, 2020 (2003)] is a powerful diagnostic that permits a two-dimensional measurement of turbulence in the edge region of a fusion plasma and is based on the observation of the local emission of a neutral gas, actively puffed into the periphery of the plasma. The developed in-vessel GPI telescope observes the emission from the puffed gas along local (at the puff) magnetic field lines. The GPI telescope is specially designed to operate in severe TEXTOR conditions and can be treated as a prototype for the GPI systems on next generation machines. Also, the gas puff nozzle is designed to have a lower divergence of the gas flow than previous GPI diagnostics. The resulting images show poloidally and radially propagating structures, which are associated with plasma blobs. We demonstrate that the local gas puff does not disturb plasma properties. Our results indicate also that the neutral gas emission intensity is more sensitive to the electron density than the electron temperature. Here, we present implementation details of the GPI system on TEXTOR and discuss some design and diagnostic issues related to the development of GPI systems in general.

A genetic determinant of the striatal dopamine response to alcohol in men.

Excessive alcohol use, a major cause of morbidity and mortality, is less well understood than other addictive disorders. Dopamine release in ventral striatum is a common element of drug reward, but alcohol has an unusually complex pharmacology, and humans vary greatly in their alcohol responses. This variation is related to genetic susceptibility for alcoholism, which contributes more than half of alcoholism risk. Here, we report that a functional OPRM1 A118G polymorphism is a major determinant of striatal dopamine responses to alcohol. Social drinkers recruited based on OPRM1 genotype were challenged in separate sessions with alcohol and placebo under pharmacokinetically controlled conditions, and examined for striatal dopamine release using positron emission tomography and [(11)C]-raclopride displacement. A striatal dopamine response to alcohol was restricted to carriers of the minor 118G allele. To directly establish the causal role of OPRM1 A118G variation, we generated two humanized mouse lines, carrying the respective human sequence variant. Brain microdialysis showed a fourfold greater peak dopamine response to an alcohol challenge in h/mOPRM1-118GG than in h/mOPRM1-118AA mice. OPRM1 A118G variation is a genetic determinant of dopamine responses to alcohol, a mechanism by which it likely modulates alcohol reward.

C-reactive protein in canine babesiosis caused by Babesia rossi and its association with outcome.

C-reactive protein (CRP) is a positive major acute-phase protein in dogs and can be used as a predictive marker for risk of disease and to monitor the response to treatment. Increased concentrations in certain diseases are associated with poor outcome. This cross-sectional, observational study of 75 dogs naturally infected with Babesia rossi was designed to examine the relationship between outcome and CRP concentration at admission and the magnitude of CRP change 24 hours after admission. Diagnosis was confirmed by polymerase chain reaction (PCR) and reverse line blot. CRP concentrations were determined by an automated human CRP Turbidometric Immunoassay, previously validated for use in dogs. There was no significant difference in mean CRP concentration between survivors (n = 57), 107.5 +/- 49.5 mg/l and non-survivors (n = 11), 122.1 +/- 64.6 mg/l at admission and using the exact logistic regression, adjusting for age and sex, there was no association with outcome (P = 0.53). Multiple regression analysis failed to show a significant relationship between admission CRP concentration and number of days of hospitalisation in the survivors, adjusting for age and sex (P = 0.65). Similarly, no significance was found in the relationship between the magnitude of change in CRP concentration 24 hours after admission, and the number of days of hospitalisation in survivors, (P = 0.34). It is concluded that CRP concentration, as a measure of the acute phase response, is not associated with outcome in canine babesiosis, and inflammation is unlikely to be the only cause of severity of disease.

A case-based, small-group cooperative learning course in preclinical veterinary science aimed at bridging basic science and clinical literacy.

In 1999 a dedicated problem-based learning course was introduced into the lecture-based preclinical veterinary curriculum of the University of Pretoria. The Introduction to Clinical Studies Course combines traditional lectures, practical sessions, student self-learning and guided tutorials. The self-directed component of the course utilises case-based, small-group cooperative learning as an educational vehicle to link basic science with clinical medicine. The aim of this article is to describe the objectives and structure of the course and to report the results of the assessment of the students' perceptions on some aspects of the course. Students reacted very positively to the ability of the course to equip them with problem-solving skills. Students indicated positive perceptions about the workload of the course. There were, however, significantly lower scores for the clarity of the course objectives. Although the study guide for the course is very comprehensive, the practice regarding the objectives is still uncertain. It is imperative to set clear objectives in non-traditional, student-centred courses. The objectives have to be explained at the outset and reiterated throughout the course. Tutors should also communicate the rationale behind problem-based learning as a pedagogical method to the students. Further research is needed to verify the effectiveness of this course in bridging the gap between basic science and clinical literacy in veterinary science. Ongoing feedback and assessment of the management and content are important to refine this model for integrating basic science with clinical literacy.

In situ measurements of calpain activity in isolated muscle fibres from normal and dystrophin-lacking mdx mice.

Calpains are Ca(2+)-activated proteases that are thought to be involved in muscle degenerative diseases such as Duchenne muscular dystrophy. Status and activity of calpains in adult muscle fibres are poorly documented. We report here in situ measurements of calpain activity in collagenase-isolated fibres from C57 mice and form two models of dystrophy: dystrophin-deficient mdx and calpain-3 knocked-out mice. Calpain activity was measured using a permeant, fluorogenic substrate and its Ca(2+) dependence was studied. A 30-fold change of activity was observed between the lowest and the highest steady-state Ca(2+) availability. Fast transient changes of [Ca(2+)](i) induced by electrical stimulation or KCl-dependent depolarization were ineffective in activating calpain. Slow [Ca(2+)] transients, as elicited during depletion of Ca(2+) stores, Ca(2+) store repletion and hypo-osmotic swelling were able to activate calpain. On return to resting conditions, calpain activity recovered its basal rate within 10 min. In resting intact muscle, mu-calpain was predominantly in the 80 kDa native form, with a small fraction in the 78 kDa autolysed form. The latter is thought to be responsible for the activity measured in our conditions. Calpain activity in mdx fibres showed an average 1.5-fold increase compared to activity in C57 fibres. This activity was reduced by a 10-fold lowering of [Ca(2+)](o). Calpain-3-deficient fibres showed about the same increase, thus calpain-3 did not contribute to the activity measured here and calpain activation is not specific to dystrophin deficiency. In fibres from transgenic mice over-expressing calpastatin, a 40-50% reduction of calpain activity was observed, as with synthetic drugs (Z-Leu-Leu-CHO and SNT198438). We provide novel information on the physiological factors that control calpain activity in situ, particularly the effect of intracellular Ca(2+) transients that occur in excitation-contraction coupling, Ca(2+) store depletion and refilling, and activation of mechanosensitive Ca(2+) channels.

Influence of the static Dynamic Ergodic Divertor on edge turbulence properties in TEXTOR.

Systematic measurements on the edge turbulence and turbulent transport have been made by Langmuir probe arrays on TEXTOR under various static Dynamic Ergodic Divertor (DED) configurations. Common features are observed. With the DED, in the ergodic zone the local turbulent flux reverses sign from radially outwards to inwards. The turbulence properties are profoundly modified by energy redistribution in frequency spectra and suppression of large scale eddies. The fluctuation poloidal phase velocity changes direction from electron to ion diamagnetic drift, consistent with the observed reversal of the Er x B flow. In the laminar region, the turbulence is found to react to an observed reduced flow shear.

Consequence of parvalbumin deficiency in the mdx mouse: histological, biochemical and mechanical phenotype of a new double mutant.

We tested the hypothesis whether the mild dystrophy in mdx mice could result from the contribution of the cytosolic calcium buffer parvalbumin in maintaining a normal cytosolic [Ca2+]i, in spite of an increased passive Ca2+ influx. By crossing mdx mice with parvalbumin-deficient mice, double mutant mice, lacking both dystrophin and parvalbumin, were obtained. Though resting cytosolic [Ca2+]i and total calcium content were similar to that of mdx muscles, this new animal model presented a slightly more severe phenotype than the mdx mouse. Muscle pseudo-hypertrophy, the density of myotubes and of centronucleated fibres as well as the loss of IIB fibres were all increased in parvalbumin-deficient mdx mice. Many of these deficits were overcome in late adulthood, albeit fibrosis was clearly more pronounced than in mdx muscles. At 90 days, parvalbumin-deficient mdx mice showed higher levels of creatine phosphokinase and lower muscle strength, in vivo, than mdx mice. Isometric tension of isolated muscle was reduced, but the susceptibility to eccentric contraction was not increased. The slight aggravation of muscle dystrophy observed in mdx mice deprived of parvalbumin cannot explain the severity of the affection observed in xmd dogs and Duchenne dystrophy patients where parvalbumin is constitutively not expressed.

Intracellular pH regulation in isolated fast-twitch skeletal muscle from dystrophin-deficient mouse.

In muscles from anaesthetized dystrophin-deficient mdx mice, exercise results in a stronger acidification and a slower intracellular pH recovery compared to control mice. We examined whether this observation could be attributed to defective H+-carriers in dystrophin-lacking muscles. Immunohistochemistry and Western blots revealed no defect in mdx muscles for the presence of the lactate-/H+co-transporter MCT4 and of the Na+/H+ antiporter NHE1, the main H+-carriers active in fast-twitch skeletal muscle after exercise. Functional tests of the H+-transporters, on isolated muscles submitted to identical flow of superfusion, were performed in conditions meant to lower intracellular pH: repetitive electrical stimulation or NH4Cl pre-pulse. These revealed no defect in intracellular pH recovery in mdx muscles. Therefore, we conclude that impaired intracellular pH regulation in anaesthetized mdx mice is not attributable to a reduced presence or activity of H+-extruders. We propose that CO2 washout might be slowed down in vivo in mdx muscles because of the defective vascular response in contracting muscles from these mice.

Involvement of trp-2 protein in store-operated influx of calcium in fibroblasts.

Mammalian homologues of the Drosophila melanogaster transient receptor potential (trp) gene have been proposed to encode store-operated channels. This assertion essentially stays on the fact that expression of different trp proteins produces trans-membrane cation currents. However, the selectivity of the expressed channels and their mode of activation, in particular, their dependence to store depletion appears to be quite variable. In the present work, we adopted an anti-sense strategy to study this question in transfected Chinese hamster ovary cells expressing the rat neurotensin receptor (CHO-NTR cells), a cellular model characterized by its very large store-dependent entry of Ca(2+). We identified different trp transcripts by RT-PCR, the trp-1 and trp-2 transcripts being by far the most abundant. CHO-NTR cells were then transfected with a mouse trp-2 anti-sense construct (CHO-NTR-TRP2AS cells). We showed that in these cells, trp-2 mRNA was suppressed in comparison with cells transfected with a control plasmid. The store-operated entry of Ca(2+) was evaluated after store depletion by an IP(3)-dependent mechanism (neurotensin stimulation) or by direct inhibition of the endoplasmic reticulum Ca(2+)ATPase (thapsigargin stimulation). In both cases, store-dependent entry of Ca(2+) was largely reduced in CHO-NTR-TRP2AS cells in comparison with control cells, suggesting that trp-2 protein might constitute a functional subunit of store-operated channels.

BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major components of plaque, beta-amyloid peptides (Abetas), are produced from amyloid precursor protein (APP) by the activity of beta- and gamma-secretases. beta-secretase activity cleaves APP to define the N-terminus of the Abeta1-x peptides and, therefore, has been a long- sought therapeutic target for treatment of AD. The gene encoding a beta-secretase for beta-site APP cleaving enzyme (BACE) was identified recently. However, it was not known whether BACE was the primary beta-secretase in mammalian brain nor whether inhibition of beta-secretase might have effects in mammals that would preclude its utility as a therapeutic target. In the work described herein, we generated two lines of BACE knockout mice and characterized them for pathology, beta-secretase activity and Abeta production. These mice appeared to develop normally and showed no consistent phenotypic differences from their wild-type littermates, including overall normal tissue morphology and brain histochemistry, normal blood and urine chemistries, normal blood-cell composition, and no overt behavioral and neuromuscular effects. Brain and primary cortical cultures from BACE knockout mice showed no detectable beta-secretase activity, and primary cortical cultures from BACE knockout mice produced much less Abeta from APP. The findings that BACE is the primary beta-secretase activity in brain and that loss of beta-secretase activity produces no profound phenotypic defects with a concomitant reduction in beta-amyloid peptide clearly indicate that BACE is an excellent therapeutic target for treatment of AD.

Tetanus relaxation of fast skeletal muscles of the mouse made parvalbumin deficient by gene inactivation.

The effects of tetanus duration on the relaxation rate of extensor digitorum longus (EDL) and flexor digitorum brevis (FDB) muscles were studied in normal (wild-type, WT) and parvalbumin-deficient (PVKO) mice, at 20 C. In EDL of PVKO, the relaxation rate was low and unaffected by tetanus duration (< 3.2 s). In contrast, the relaxation rate of WT muscles decreased when tetanus duration increased from 0.2 to 3.2 s. In WT muscles, fast relaxation recovered as the rest interval increased. Specific effect of parvalbumin was asserted by calculating the difference in relaxation rate between WT and PVKO muscles. For EDL, the rate constant of relaxation slowing was 1.10 s-1 of tetanization; the rate constant of relaxation recovery was 0.05 s-1 of rest. In FDB, the effects of tetanus duration on WT and PVKO muscles were qualitatively similar to those observed in EDL. Relaxation slowing as tetanus duration increases, reflects the progressive saturation of parvalbumin by Ca2+, while recovery as rest interval increases reflects the return to Ca2+-free parvalbumin. At all tetanus durations, relaxation rate still remained slightly faster in WT muscles. This suggested that parvalbumin facilitates calcium traffic from myofibrils to the SR. No difference was found between WT and PVKO muscles for: (i) the expression of the fast isoforms of myosin heavy chains, (ii) the force-velocity relationship and maximal shortening velocity and (iii) the Ca2+-activated ATPase activity from isolated preparations of the sarcoplasmic reticulum (SR).

Skeletal dysplasias, growth retardation, reduced postnatal survival, and impaired fertility in mice lacking the SNF2/SWI2 family member ETL1.

The mouse Etl1 gene encodes a nuclear protein belonging to the rapidly growing SNF2/SWI2 family. Members of this family are related to helicases and nucleic-acid-dependent ATPases and have functions in essential cellular processes such as transcriptional regulation, maintenance of chromosome stability and various aspects of DNA repair. The ETL1 protein is expressed from the two-cell stage onwards, throughout embryogenesis in a dynamic pattern with particularly high levels in the thymus, epithelia and the nervous system and in most adult tissues. As a first step to address the role of ETL1 in cells and during development, we inactivated the gene by homologous recombination. ES cells and mice lacking detectable ETL1 protein were viable, indicating that ETL1 is not essential for cell survival or for embryonic development. However, mutant mice showed retarded growth, peri/post natal lethality, reduced fertility and various defects in the sternum and vertebral column. Expressivity and penetrance of all observed phenotypes were influenced by the genetic background. Isogenic 129Sv(Pas) mice lacking ETL1 had a severely reduced thoracic volume, which might lead to respiratory failure and could account for the high incidence of perinatal death on this genetic background.

Astronaut-induced disturbances in microgravity.

This Note describes the dynamic load sensors (DLS) spaceflight experiment that measured middeck astronaut-induced disturbances during the 14-day STS-62 Space Shuttle mission in March 1994. The DLS experiment was flown in conjunction with the reflight of the Middeck 0-Gravity Dynamics Experiment (MODE). The objective of MODE was to investigate effects of the microgravity environment on large space structures. Where Skylab experiments focused on measuring the forces exerted during vigorous soaring activities, the DLS experiment quantified the reaction forces and moments exerted by the crew going about their normal on-orbit activities. The objective of this Note is to present DLS force data and frequency analysis that characterize astronaut-induced loads during spaceflight.

Lack of myoblasts migration between transplanted and host muscles of mdx and normal mice.

Extensor digitorum longus muscles of normal mice (C57BL/10ScSn hereafter called C57) were orthotopically transplanted into dystrophin-deficient mice (mdx) and reciprocally, mdx Extensor digitorum longus muscles were transplanted into C57 mice. After an initial phase of degeneration, transplanted muscles regenerate nearly completely, as evaluated from the maximum isometric force of muscles isolated 60 days after the surgery. In other similar experiments, instead of isolating the grafted muscles, we excised the antero-external muscles of the leg, including the grafted muscle. Cryostat cross-sections at three levels along the muscles were immunostained with an anti-dystrophin antibody. No muscle cells of dystrophin-deficient muscles grafted into normal mice took the antibody except a few 'revertant' fibres, while all the muscle cells of the normal host were immunostained. Reciprocally, all the muscles cells of normal grafts were stained, whilst no antibody stained the cells of the surrounding muscles of the dystrophin-deficient host. These experiments show that very few if any of the myoblasts or muscle precursor cells, active during the regeneration of grafted muscle, migrate into the adjacent muscles. These results could be explained by the absence, in our work, of injuries of the grafted and adjacent host muscles epimysium and the absence of extensive inflammatory reactions. This lack of myoblast mobility suggest that when myoblast transfer is applied to muscle therapy, it will be necessary to inject myoblasts within each muscle to obtain an efficient treatment.

The Etl-1 gene encodes a nuclear protein differentially expressed during early mouse development.

Recently, we isolated a novel mouse gene, Etl-1 (Enhancer-trap-locus-1), whose deduced amino acid sequence shows in its C-terminal portion striking homology to the brahma protein (BRM), a transcriptional regulator of homeotic genes in Drosophila, and to SNF2/SWI2, a transcriptional regulator of various genes in Saccharomyces cerevisiae. Here we report the generation of antibodies against the Etl-1 gene product (ETL-1) and describe the subcellular localization as well as the expression and distribution of the ETL-1 protein during mouse pre- and early post-implantation development. ETL-1 is a nuclear protein and is expressed in a biphasic manner during early embryogenesis. Moderate levels of ETL-1 were detected in unfertilized and fertilized eggs but in the latter the protein was not concentrated in the pronuclei and seemed evenly distributed throughout the cytoplasm. In two-cell embryos nuclear ETL-1 protein accumulated transiently and levels decreased during subsequent cleavage development. After the morula stage, ETL-1 levels increased again; in blastocysts high levels of ETL-1 were present in inner cell mass cells whereas trophectoderm cells contained little or no ETL-1. During subsequent development essentially all cell types except parietal endoderm and trophoblast cells contained high levels of ETL-1. Our results imply that nuclear ETL-1 is dispensable for the progression to the two cell stage, and suggest that during cleavage ETL-1 might be needed at the onset of embryonic transcription. In blastocysts ETL-1 function might be specifically required in cells of the inner cell mass and later in most cells of the embryo proper and extraembryonic ectoderm lineage.