Phospholamban cardiomyopathy: a Canadian perspective on a unique population.

INTRODUCTION: Phospholamban cardiomyopathy is an inherited cardiomyopathy, characterised by a defect in regulation of the sarcoplasmic reticulum Ca2+ pump, often presenting with malignant arrhythmias and progressive cardiac dysfunction occurring at a young age. METHODS: Phospholamban R14del mutation carriers and family members were identified from inherited arrhythmia clinics at 13 sites across Canada. Cardiac investigations, including electrocardiograms, Holter monitoring (premature ventricular complexes, PVCs), and imaging results were summarised. RESULTS: Fifty patients (10 families) were identified (median age 30 years, range 3-71, 46% female). Mutation carriers were more likely to be older, have low-voltage QRS, T­wave inversion, frequent PVCs, and cardiac dysfunction, compared to unaffected relatives. Increasing age, low-voltage QRS, T­wave inversion, late potentials, and frequent PVCs were predictors of cardiac dysfunction (p < 0.05 for all). Older carriers (age ≥45 years) were more likely to have disease manifestations than were their younger counterparts, with disease onset occurring at an older age in Canadian patients and their Dutch counterparts. DISCUSSION: Among Canadian patients with phospholamban cardiomyopathy, clinical manifestations resembled those of their Dutch counterparts, with increasing age a major predictor of disease manifestation. Older mutation carriers were more likely to have electrical and structural abnormalities, and may represent variable expressivity, age-dependent penetrance, or genetic heterogeneity among Canadian patients.

Colonization dynamic of various crop residues by Fusarium graminearum monitored through real-time PCR measurements.

AIMS: To evaluate the effect of the type of crop residues on the colonization dynamic of Fusarium graminearum in soil. METHODS AND RESULTS: The ability of F. graminearum to survive in the presence of various crop residues was assessed on Petri dishes and in microcosms. These microcosms comprised soil that had or had not been previously disinfested with or without amendment with various crop residues. The colonization dynamic of F. graminearum was monitored through real-time PCR. Fusarium graminearum development was higher in disinfested soil than in non-disinfested one. The fungal growth was enhanced to various extents according to the type of crop residues, except for mustard residues which inhibited it. The biochemical and physical properties of the residues were likely to account for the differences in the survival of F. graminearum. CONCLUSIONS: Fusarium graminearum is a poor competitor in soil but it can use maize, wheat, and rape residues to ensure its survival. Conversely alfalfa, which is assimilated by micro-organisms very easily, avoids long-lasting survival of the fungus. And finally, mustard producing glucosinolates could be used as an intermediate crop to reduce the inoculum amount. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is contributing to the knowledge about F. graminearum saprotophic abilities and proposes interesting paths to limit its survival in soil.

Plant genotype and nitrogen loading influence seagrass productivity, biochemistry, and plant-herbivore interactions.

Genetic variation within and among key species can have significant ecological consequences at the population, community, and ecosystem levels. In order to understand ecological properties of systems based on habitat-forming clonal plants, it is crucial to clarify which traits vary among plant genotypes and how they influence ecological processes, and to assess their relative contribution to ecosystem functioning in comparison to other factors. Here we used a mesocosm experiment to examine the relative influence of genotypic identity and extreme levels of nitrogen loading on traits that affect ecological processes (at the population, community, and ecosystem levels) for Zostera marina, a widespread marine angiosperm that forms monospecific meadows throughout coastal areas in the Northern Hemisphere. We found effects of both genotype and nitrogen addition on many plant characteristics (e.g., aboveground and belowground biomass), and these were generally strong and similar in magnitude, whereas interactive effects were rare. Genotypes also strongly differed in susceptibility to herbivorous isopods, with isopod preference among genotypes generally matching their performance in terms of growth and survival. Chemical rather than structural differences among genotypes drove these differences in seagrass palatability. Nitrogen addition uniformly decreased plant palatability but did not greatly alter the relative preferences of herbivores among genotypes, indicating that genotype effects are strong. Our results highlight that differences in key traits among genotypes of habitat-forming species can have important consequences for the communities and ecosystems that depend on them and that such effects are not overwhelmed by known environmental stressors.

Evaluation of Nonpathogenic Fusarium oxysporum and Pseudomonas fluorescens for Panama Disease Control.

Nonpathogenic Fusarium oxysporum endophytes from healthy banana roots were evaluated for their ability to reduce Fusarium wilt of banana (Panama disease). Isolates were identified morphologically and by using species-specific primers. Pathogenicity was confirmed by inoculating banana plantlets in the greenhouse. Nonpathogenic F. oxysporum isolates were grouped into 14 haplotype groups by polymerase chain reaction restriction fragment length polymorphism analysis of the intergenic spacer region, and representative isolates evaluated for biocontrol of F. oxysporum f. sp. cubense. In the greenhouse, 10 nonpathogenic F. oxysporum isolates were able to significantly reduce Fusarium wilt of banana. The isolate that protected banana plantlets best in the greenhouse, a nonpathogenic F. oxysporum from the root rhizosphere, and Pseudomonas fluorescens WCS 417 were then field tested. When the putative biological control organisms were tested in the field, neither the nonpathogenic F. oxysporum, P. fluorescens, nor combinations thereof reduced Fusarium wilt development significantly. A number of factors could contribute to the lack of field protection, including soil microbial and chemical composition and reduced survival of biocontrol organisms in banana roots. A lack of knowledge regarding the etiology of Fusarium wilt of 'Cavendish' banana in the subtropics and the effect of F. oxysporum f. sp. cubense race and banana cultivar in protection of banana by biocontrol organisms should be further investigated.

Natural organic matter (NOM) has the potential to modify the multixenobiotic resistance (MXR) activity in freshwater amphipods Eulimnogammarus cyaneus and E. verrucosus.

Based on the chemical features of natural organic matter (NOM) with its variety of functional groups, we hypothesized that NOM will modify the multixenobiotic-resistance (MXR) of an organism as xenobiotic chemicals do. The MXR system is a general first rather non-specific line of defense against environmental contaminants. The aim of this study was to compare the impacts on MXR activity in amphipod species (Eulimnogammarus cyaneus and E. verrucosus, from Lake Baikal) stressed by cadmium chloride or dissolved NOM for 24 h. NOM exposure concentrations were environmentally realistic. MXR activity was assessed based on rhodamine B efflux; its specificity was proven by a verapamil inhibition assay. It was shown that both NOM and CdCl(2) lead to substantial reduction of the rhodamine B efflux. This suggests that NOM may be regarded as a chemosensor which is able to reduce the efficiency of the MXR system. Possible mechanisms of direct NOM impact on MXR processes are discussed, such as peroxidation of the membranes (including P-glycoproteins) or internal blockage of the MXR pump by bioconcentrated NOM. In general, our results show that well-developed depuration pathways of freshwater organisms in contaminated environments may be impaired by strong chemical stressors and, more important, by natural biogeochemical matrices such as humic substances--humic substances are present in all freshwater systems.

Review of solutions for 3D hydrodynamic modeling applied to aquaculture in South Pacific atoll lagoons.

A workshop organized in French Polynesia in November 2004 allowed reviewing the current methods to model the three-dimensional hydrodynamic circulation in semi-enclosed atoll lagoons for aquaculture applications. Mollusk (e.g. pearl oyster, clam) aquaculture is a major source of income for South Pacific countries such as French Polynesia or Cook Islands. This aquaculture now requires a better understanding of circulation patterns to improve the spatial use of the lagoons, especially to define the best area to set larvae collectors. The pelagic larval duration of the relevant species (<20 days) and the size of the semi-closed lagoons (few hundreds of km2) drive the specifications of the model in terms of the spatial and temporal scale. It is considered that, in contrast with fish, mollusk larvae movements are limited and that their cycle occurs completely in the lagoon, without an oceanic stage. Atolls where aquaculture is productive are generally well-bounded, or semi-closed, without significant large and deep openings to the ocean. Nevertheless part of the lagoon circulation is driven by oceanic water inputs through the rim, ocean swells, tides and winds. Therefore, boundary conditions of the lagoon system are defined by the spatial structure of a very shallow rim (exposition and number of hoas), the deep ocean swell climate, tides and wind regimes. To obtain a realistic 3D numerical model of lagoon circulation with adequate forcing, it is thus necessary to connect in an interdisciplinary way a variety of methods (models, remote sensing and in situ data collection) to accurately represent the different components of the lagoon system and its specific boundary conditions. We review here the current methods and tools used to address these different components for a hypothetical atoll of the Tuamotu Archipelago (French Polynesia), representative of the semi-closed lagoons of the South Pacific Ocean. We hope this paper will serve as a guide for similar studies elsewhere and we provide guidelines in terms of costs for all the different stages involved.

Antioxidant response to natural organic matter (NOM) exposure in three Baikalean amphipod species from contrasting habitats.

The aim of the present work is to comparatively evaluate the oxidative stress response on exposure to natural organic matter (NOM) in three amphipod (Crustacea, Amphipoda) species from different taxonomic groups and different habitats of Lake Baikal. Endemic species from Lake Baikal were used: the shallow-water dwelling Gmelinoides fasciatus (Dyb.), Pallasea cancelloides (Gerstf.), and the deep-layer inhabitant Ommatogammarus flavus (Dyb.). Three key enzymes, catalase (CAT), peroxidase (POD), and glutathione S-transferase (GST), were studied. The applied NOM from Lake Schwarzer (Germany) directly impacts the two littoral species which quickly respond. The response is characterized by a significant decrease of POD and an increase of CAT activities. GST activity remains stable or decreased slightly. In contrast to the littoral amphipods, the deep-layer inhabitant O. flavus showed no significant reaction to NOM exposure, probably due to decreased adaptive ability of this species. The stable environment of the Baikalean deep zones obviously does not provide triggers for the development of flexible antioxidant or general defense systems.

Dissolved natural organic matter (NOM) impacts photosynthetic oxygen production and electron transport in coontail Ceratophyllum demersum.

Dissolved natural organic matter (NOM) is dead organic matter exceeding, in freshwater systems, the concentration of organic carbon in all living organisms by far. 80-90% (w/w) of the NOM is made up of humic substances (HS). Although NOM possesses several functional groups, a potential effect on aquatic organisms has not been studied. In this study, direct effects of NOM from various origins on physiological and biochemical functions in the aquatic plant Ceratophyllum demersum are presented. Environmentally relevant concentrations of NOM cause inhibitory effects on the photosynthetic oxygen production of C. demersum. Various NOM sources and the synthetic humic substance HS1500 inhibit the photosynthetic oxygen production of the plant as observed with 1-amino-anthraquinone, a known inhibitor of plant photosynthesis. 1-Aminoanthraquinone may serve as an analogue for the quinoid structures in NOM and HS. Most likely, the effects of NOM may be related to quinoid structures and work downstream of photosynthesis at photosystem (PS) II.

Direct and interacting toxicological effects on the waterflea (Daphnia magna) by natural organic matter, synthetic humic substances and cypermethrin.

Humic substances are the main component of dissolved organic matter in all aquatic ecosystems, comprising a variety of molecular structures and functional groups. They bind organic pollutants and metals, thereby decreasing the bioavailability and consequently the toxicity of these substances in most instances. Recent studies also describe direct interactions and effects on organisms. Current studies also show that in some cases mitigation effects are stronger at lower concentrations of natural organic matter (NOM) and that toxicity increases with increased NOM concentrations. We hypothetise that at higher concentrations the mitigating effects are overlayed by direct effects of NOM themselves, thus these aspects were investigated in combination. So, on the one hand, this study demonstrates direct effects on toxicological parameters and activities of transformation enzyme systems of Daphnia magna, provoked by two NOM and one synthetic humic-like substance, HS1500. On the other hand, capacities of NOM and synthetic HS1500 to mitigate effects of the insecticide cypermethrin were investigated. Taken together, mitigation effects were overlayed by direct own effects of the NOM and HS1500. The NOM used were isolates from Suwannee River (XAD, Spring 2000) and from streams of the Svartberget forest (reverse osmosis, Spring 2000). The HS1500 was synthetically produced by radicalic autoxidation of hydroquinones. Suwannee River NOM at concentrations between 50 and 100 mg/l, and HS1500 (10-50 mg/l), but not Svartberget NOM increased immobility and lethality of the daphnids. All elevated the activity of the soluble glutathione S-transferase from 0.5 mg/l (HS1500), 1.0 mg/l (Suwannee River NOM) and 10 mg/l (Svartberget NOM) onwards, the microsomal glutathione S-transferase did not react. The glutathione peroxidase tended to increase. In the single exposure, the insecticide cypermethrin increased all toxicological parameters, elevated soluble and tendentially microsomal glutathione S-transferase activity between 0.001 and 1.0 microg/l and tendentially increased glutathione peroxidase. In contrast to that, 50 mg/l of the NOM and HS1500 did not mitigate toxicological effects. HS1500 in combination with cypermethrin even increased immobility, compared to cypermethrin alone. Increase of the NOM or HS1500 concentrations in combination with cypermethrin did not increase mitigation as seen in the activity of soluble glutathione S-transferases, activities of microsomal glutathione S-transferase and glutathione peroxidase even decreased, relative to control, which can be a hint of enzyme disfunction or further damages in the cell. An increase of concentration did not increase mitigation. Mitigation was higher at lower NOM or HS1500 concentration, probably as a consequence of the direct effects caused by themselves. Consequently, direct effects are relevant for analysing the mitigation qualities.

Sustainable development--assessment of water resource management measures.

An approach is presented which supports decision makers in the field of water resource management to create and evaluate alternative strategies in the context of goals based on in sustainable development. The broad range of water resource management activities demand a highly structured methodology. The building blocks of the assessment procedure range from the characterization of the status quo to the development and application of assessment aids to perform exemplary evaluations.

Applying the concept of partially ordered sets on the ranking of near-shore sediments by a battery of tests.

When a ranking of some objects (chemicals, geographical sites, river sections, etc.) by a multicriteria analysis is of concern, then it is often difficult to find a common scale among the criteria, and therefore even the simple sorting process is performed by applying additional constraints, just to get a ranking index. However such additional constraints, often arising from normative considerations, are controversially discussed. The theory of partially ordered sets and its graphical representation (Hasse diagrams) does not need such additional information just to sort the objects. Here, the approach of using partially ordered sets is described by applying it to a battery of tests, developed by Dutka et al. In our analysis we found the following: (1) The dimension analysis of partially ordered sets suggests that, at least in the case of the 55 analyzed samples and the evaluation by the scores, developed by Dutka et al., there is a considerable redundancy with respect to ranking. The visualization of the sediment sites can be performed within a two-dimensional grid. (2) Information, obtained from the structure of the Hasse diagram: For example six classes of sediment sites have high priority, and each class exhibits a different pattern of results. (3) Loss of information, when an aggregation of test results is used in order to guarantee complete comparability among all objects. A relation between information drawn from the graphic and the uncertainty of ranking after using an aggregation is given. (4) The sensitivity analysis identifies one test as most important, namely the test for Fecal Coliforms/Escherichia coli. This means that the ranking of samples is heavily influenced by the results of this specific test.

Interaction of cadmium toxicity in embryos and larvae of zebrafish (Danio rerio) with calcium and humic substances.

The influence of humic substances (HS) and calcium (Ca) on cadmium (Cd) toxicity was determined using zebrafish (Danio rerio). Embryo and larvae of the zebrafish were exposed to various Cd concentrations (1.8; 2.8; 4.2; 6.2; 9.3 mg/l Cd) for 144 h. Combinations of low (0.2 mmol/l) and high (2 mmol/l) Ca, +HS (5 mg/l C) or -HS were used during Cd exposure. The toxicity of Cd was affected by (1) exposure concentration; (2) exposure time; (3) presence of HS; and (4) the Ca concentration. The results show that Ca and HS protect against Cd toxicity in zebrafish embryos. The best protection was in the high Ca-HS group, followed by high Ca+HS group and low Ca+HS group. The survival in the low Ca-HS group was the worse. Survival in the high Ca-HS group and the high Ca+HS group was similar with the exception of the highest Cd concentration (9.3 mg/l) where the survival of the high Ca+HS group was less than in the high Ca-HS group. The exposure system was modelled using a chemical equilibrium program (MINEQL+) to determine if the likely mechanism causing the anomalous result in the highest Cd concentration. The equilibrium model cannot explain these results, which suggests that this effect has a kinetic basis, such as time needed for Cd to displace Ca already bound by HS.

Influence of aqueous sediment extracts from the Oder River (Germany/Poland) on survival of Diplostomum sp. (Trematoda: Diplostomidae) cercariae.

Laboratory experiments were carried out to test whether the life span of Diplostomum sp. cercariae is affected by contamination of its aquatic environment. Freshly emerged cercariae therefore were exposed to either standardized water, Oder River (Germany/Poland) or Lake Odersee (Germany) extracts of aqueous sediments; mortality patterns and mean survival times (MSTs) were compared. Cercariae added to extracts of aqueous sediments from the Oder River and Lake Odersee exhibited impaired survival with significantly different mortality pattern and reduced MST compared to that of controls. A significant negative correlation (r = -0.843, p < 0.05) was found between MST and mercury content of sediments, indicating a potential impact of mercury on survival of Diplostomum sp. cercariae. The results indicate that contamination of freshwater habitats may influence the viability of free-living transmission stages of helminth parasites of fish and may thus be of epizootiological significance.

No enhancement in bioconcentration of organic contaminants by low levels of DOM.

The aim of the present work was to systematically study the effect of low concentrations of dissolved organic matter (DOM) on the bioconcentration of organic contaminants, in order to show whether the phenomenon of enhanced bioconcentration factors (BCFs), that has been reported in the literature, is generally found at low levels of DOM or if BCF enhancements are more likely due to a random scatter in the experimental data. The first part of the study tested the hypothesis that low levels of DOM affect the uptake kinetics of organic contaminants, leading to transient enhancements of BCFs, relative to DOM-free controls, which could have been reported as BCF enhancements in short-term studies. We found that the presence of low concentrations of two different types of DOM consistently decreased the bioconcentration of benzo[a]pyrene (BaP) in the water flea Daphnia magna at all exposure times (1-24 h), and that no transient BCF enhancements occurred. The second part of the study systematically investigated if low concentrations of DOM from a wide range of different aquatic systems can cause enhancements in the bioconcentration of organic contaminants. Water fleas were exposed to combinations of four different organic contaminants (BaP, tetrachlorobiphenyl, pentachlorophenol and naphthalene) with low concentrations of 12 different types of DOM that had been collected from various regions throughout Europe. In several of the DOM treatments, we found mean BCFs being higher than mean BCFs in the controls (especially for naphthalene). This shows that the experimental setup used in this study (and similarly in previous studies) can produce seeming BCF enhancements at low concentrations of DOM. However, statistical analyses showed that treatment means were not significantly different from control means. Thus, this systematic study suggests that the BCF enhancements that have been reported in the literature are more likely the result of random, experimental variations than the result of a systematic enhancement of bioconcentration.

Toxicokinetics of atrazine in embryos of the zebrafish (Danio rerio).

Atrazine (2-chloro-4-ethylamino-6-isopropylamine-s-triazine) is a widely used selective herbicide. Due to its persistence, it is present in many surface waters, contaminating nontarget organisms such as fish. Teratogeny of atrazine was examined during the first 48 h of zebrafish development (embryo test) and correlated to effects on the microsomal and soluble glutathione S-transferases (m-/sGST; EC 2.5.1.18). Atrazine at 4 mg/L disturbed the normal development to long pec stage, at concentrations between 10 and 20 mg/L it caused retardations in organogenesis, a slowdown of movements, and functional disturbances of heart and circulatory system. m- and sGST activities were affected by atrazine in all investigated developmental stages. Atrazine elevated the mGST activity dose dependently up to a concentration of 5 mg/L, and the sGST up to 1 mg/L. Higher atrazine concentrations caused a decrease of GST activity, especially of the sGST of the younger stages, 32 cells and 75% epiboly. This might indicate that the detoxication system itself is affected, which then gives rise to morphological abnormalities during fish development. In vitro tests were performed to purify and characterize GST-formed atrazine metabolites by the use of ESI--HPLC--MS. mGST showed higher conversion rates compared to sGST.

Uptake, effects, and metabolism of cyanobacterial toxins in the emergent reed plant Phragmites australis (cav.) trin. ex steud.

The commonly occurring cyanobacterial toxin microcystin-LR (MC-LR) was rapidly taken up by the emergent reed plant Phragmites australis with clear distribution in the different cormus parts of the plant. Highest uptake was detected in the stem, followed by the rhizome. Enzyme extracts of the rhizome system, the stem, and the leaf revealed the presence of soluble glutathione S-transferases (sGST) measured with the model substrate 1-chloro-2,4-dinitrobenzene. A significant elevation of sGST activity in the rhizome and stem parts of P. australis was detected after a 24-h exposure to 0.5 microg/L MC-LR. Rhizome, stem, and leaf tissues were also able to conjugate several microcystin toxins. However, no conjugation, either chemical nor enzymatic, was detected using the related cyanobacterial toxin nodularin as substrate. Highest glutathione S-transferase activity for the toxin substrates was detected in the pkat/mg range in the stem of P. australis. For MC-LR, a complete metabolism from the formation of a glutathione conjugate to the degradation of a cysteine conjugate in all cormus parts of the plant is reported. The stepwise degradation of the MC-LR-glutathione conjugate to a gamma-glutamylcysteine and a cysteine conjugate was demonstrated by comparison with chemically formed reference compounds and by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. This is the first evidence for the uptake and metabolism of cyanobacterial toxins by an emergent aquatic macrophyte.

Genetic diversity of Fusarium oxysporum populations isolated from different soils in France.

The genetic diversity of soil-borne populations of Fusarium oxysporum was assessed using 350 isolates collected from six different French soils. All isolates were characterised by restriction fragment analysis of the PCR-amplified ribosomal intergenic spacer (IGS). Twenty-six IGS types were identified among the 350 isolates analysed. Five to nine different IGS types were detected in each soil. None of the IGS types was common to all of the soils. An analysis of the molecular variance based on IGS type relationships and frequency revealed that the genetic structure of the populations of F. oxysporum varied widely among the soils. Some populations were both highly diverse within the soils and differentiated between the soils. A possible relationship between the intrapopulation or interpopulation level of diversity and some external factors such as the soil type or the crop history was evaluated. A subsample representative of the diversity of the six populations was further characterised by analysing the genomic distribution of two transposable elements, impala and Fot1. One to 10 copies of the impala element were present in most of the isolates, irrespective of their soil of origin. The Fot1 element was only detected in 40% of the isolates originating from the three populations less diverse in terms of IGS types, but in 82.6% of the isolates originating from the three more diverse populations.

Benefits of lifestyle modification in the pharmacologic treatment of obesity: a randomized trial.

BACKGROUND: Weight loss medications are recommended as an adjunct to diet and exercise modification but seem to be prescribed as a monotherapy by many physicians. This practice is likely to be associated with suboptimal weight loss. METHODS: This 1-year, randomized trial compared the effects of sibutramine hydrochloride used alone (ie, the drug-alone group) to sibutramine plus group lifestyle modification, prescribed with either a 5021- to 6276-kJ/d diet (1200-1500-kcal/d diet) (ie, the drug-plus-lifestyle group) or, for the first 4 months, a 4184-kJ/d diet (1000-kcal/d diet (ie, drug-plus-lifestyle with a portion-controlled diet [the combined treatment] group). Participants were 53 women with a mean (+/-SD) age of 47.2 +/- 9.8 years and weight of 101.3 +/- 9.7 kg. At baseline, they reported the number of pounds they expected to lose at the end of treatment. RESULTS: At month 12, patients treated with the drug alone lost (mean +/- SD) 4.1% +/- 6.3% of their initial body weight compared with significantly (P<.05) larger losses in the drug-plus-lifestyle group of 10.8% +/- 10.3% and the combined treatment group of 16.5% +/- 8.0%. Women in the 2 lifestyle groups achieved a significantly (P<.05) greater percentage of their expected weight loss than those in the drug-alone group and were significantly more satisfied with the medication and with changes in weight, health, appearance, and self-esteem (P<.05 for all). Significant reductions were observed at 12 months in triglyceride and low-density lipoprotein cholesterol levels but systolic and diastolic blood pressure both increased significantly (P<.05 for all). CONCLUSION: The addition of group lifestyle modification to the pharmacologic management of obesity significantly improved weight loss and patients' satisfaction with treatment outcome.