Niveau de contamination par le mercure des sédiments de surface et des crevettes du fjord du Saguenay

De 1947 à 1976, plusieurs dizaines de tonnes de mercure d'origine industrielle ont été déversées dans les eaux de la rivière Saguenay et une grande partie de ce métal toxique se retrouve aujourd'hui dans les sédiments du Fjord. Les sédiments de surface (0-2 cm) de 17 stations réparties sur tout le bassin intérieur du fjord ont été prélevés et analysés pour le mercure total. De plus, environ 150 crevettes (Pandalus borealis) ont été capturées à Sainte-Rose-du-Nord pour fins d'analyse du mercure et pour une expérience de bioaccumulation à partir d'une diète contaminée. L'analyse des données disponibles pour les sédiments de surface montre que les teneurs moyennes (0,93 ± 0,11 µg.g-1 poids sec) en mercure n'ont pas varié de façon significative au cours des dix dernières années dans la région de Sainte-Rose-du-Nord, située dans la moitié amont du bassin intérieur. Les concentrations de mercure dans le muscle comestible des crevettes varient de 0,13 à 0,58 µg.g-1 (poids humide) selon la taille avec une valeur moyenne de 0,36 ± 0,11 µg.g-1. On trouve une concentration moyenne de 0,26 ± 0,09 µg.g-1 dans le céphalothorax et la cuticule. Un accroissement rapide et important du mercure dans, l'appareil digestif a été observé chez tes crevettes adultes soumises à une diète de chair de moules préalablement contaminée (6,0 ± 1,0 µg.g-1). Un taux de bioaccumulation de 0,09 µg.g-1 par jour dans le muscle comestible a été estimé pour les 14 premiers jours de diète contaminée.From 1947 to 1976, many tons of industrial mercury were tipped into the Saguenay River and a large amount of this toxic heavy metal is now in the sediments of the Saguenay Fjord. Surface sediments (0-2 cm) were collected at seventeen stations along the inner basin of the Saguenay Fjord and analysed for total mercury content. About 150 shrimps (Pandalus borealis) fished in the Sainte-Rose-du-Nord area were also used for mercury analyses and the determination of mercury uptake rate from contaminated food. The mercury concentrations in surface sediments ranged from 0.18 to 0.20 µg.g-1 (dry weight) with a mean value of 0.63 µg.g-1. This mean level is about one order of magnitude higher than the background level found in deep sediments. The examination of available data for surface sediments in the Sainte-Rose-du-Nord vicinity, located in the first half of the inner basin, shows the "steady state" of the mercury contamination over the last 10 years. Indeed, the mercury concentrations observed in surface sediments ranged from 0.75 to 1.20 µg.g-1, with a mean value of 0.93 µg.g-1 since 1976. The steady state of mercury contamination can be explained by two hypothesis : (1) an unexpected highly active bioturbation mechanism contributes to the mercury remobilisation from lower sediment layers (10-20 cm) and its vertical transportation up to the surface, or (2) the anthropogenic upstream discharge of mercury was not really stopped in 1976 and one or many unidentified sources are still active along the Saguenay River. The mercury concentrations in the edible part of shrimps (fished in November 1985) ranged from 0.13 to 0.58 µg.g-l (wet weight) with an average value of 0.36 ± 0.11 µg.g-1. A positive and significative linear relationship (r = 0.786) is observed between the Hg concentration in the edible part and the total wet weight of the shrimp. The mean Hg in the edible part found in 1985 is not significantly different from the mean value reported in 1932. The mean concentration found in the cephalothorax and the cuticle (taken together) of shrimps was 0.26 ± 0.09 µg.g-1. In order to estimate the mercury uptake rate by shrimps from contaminated food, a number of adult shrimps were fed with pre-contaminated mussel tissues (0.6 ± 1.0 µg.g-1) for three weeks. A high and rapid increase of mercury concentration was observed in the digestive organs after only 24 hours. The uptake rate in the edible part was estimated at 0.09 µg.g-1 per day during the first fourteen days of the bioassay. These findings clearly indicate the fragility of the balance between the biota and the physical environment and how fast major changes can occur when the level of contamination of the diet is modified

Autonomic Nervous System and Neurocardiac Physiopathology

The autonomic nervous system regulates multiple physiological functions; how distinct neurons in peripheral autonomic and intrathoracic ganglia communicate remains to be established. Increasing focus is being paid to functionality of the neurocardiac axis and crosstalk between the intrinsic nervous system and diverse organ systems. Current findings indicate that progression of cardiovascular disease comprises peripheral and central aspects of the cardiac nervous system hierarchy. Indeed, autonomic neuronal dysfunction is known to participate in arrhythmogenesis and sudden cardiac death; diverse interventions (pharmacological, non-pharmacological) that affect neuronal remodeling in the heart following injury caused by cardiovascular disease (congestive heart failure, etc.) or acute myocardial infarction are being investigated. Herein we examine recent findings from clinical and animal studies on the role of the intrinsic cardiac nervous system on regulation of myocardial perfusion and the consequences of cardiac injury. We also discuss different interventions that target the autonomic nervous system, stimulate neuronal remodeling and adaptation, and thereby optimize patient outcomes

Augmentation of tibial plateau fractures with Trabecular Metal™: a biomechanical study

<p>Abstract</p> <p>Background</p> <p>Restoration and maintenance of the plateau surface are the key points in the treatment of tibial plateau fractures. Any deformity of the articular surface jeopardizes the future of the knee by causing osteoarthritis and axis deviation. The purpose of this study is to evaluate the effect of Trabecular Metal (porous tantalum metal) on stability and strength of fracture repair in the central depression tibial plateau fracture.</p> <p>Method</p> <p>Six matched pairs of fresh frozen human cadaveric tibias were fractured and randomly assigned to be treated with either the standard of treatment (impacted cancellous bone graft stabilized by two 4.5 mm screws under the comminuted articular surface) or the experimental method (the same screws supporting a 2 cm diameter Trabecular Metal (TM) disc placed under the comminuted articular surface). Each tibia was tested on a MTS machine simulating immediate postoperative load transmission with 500 Newton for 10,000 cycles and then loaded to failure to determine the ultimate strength of the construct.</p> <p>Results</p> <p>The trabecular metal construct showed 40% less caudad displacement of the articular surface (1, 32 ± 0.1 mm vs. 0, 80 ± 0.1 mm) in cyclic loading (p < 0.05). Its mechanical failure occurred at a mean of 3275 N compared to 2650 N for the standard of care construct (p < 0, 05).</p> <p>Conclusion</p> <p>The current study shows the biomechanical superiority of the trabecular metal construct compared to the current standard of treatment with regards to both its resistance to caudad displacement of the articular surface in cyclic loading and its strength at load to failure.</p

The impact of phenotypic and genetic heterogeneity on results of genome wide association studies of complex diseases

Phenotypic misclassification (between cases) has been shown to reduce the power to detect association in genetic studies. However, it is conceivable that complex traits are heterogeneous with respect to individual genetic susceptibility and disease pathophysiology, and that the effect of heterogeneity has a larger magnitude than the effect of phenotyping errors. Although an intuitively clear concept, the effect of heterogeneity on genetic studies of common diseases has received little attention. Here we investigate the impact of phenotypic and genetic heterogeneity on the statistical power of genome wide association studies (GWAS). We first performed a study of simulated genotypic and phenotypic data. Next, we analyzed the Wellcome Trust Case-Control Consortium (WTCCC) data for diabetes mellitus (DM) type 1 (T1D) and type 2 (T2D), using varying proportions of each type of diabetes in order to examine the impact of heterogeneity on the strength and statistical significance of association previously found in the WTCCC data. In both simulated and real data, heterogeneity (presence of "non-cases") reduced the statistical power to detect genetic association and greatly decreased the estimates of risk attributed to genetic variation. This finding was also supported by the analysis of loci validated in subsequent large-scale meta-analyses. For example, heterogeneity of 50% increases the required sample size by approximately three times. These results suggest that accurate phenotype delineation may be more important for detecting true genetic associations than increase in sample size

Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Poly(ADP-ribose) polymerases (PARPs) catalyze the formation of poly(ADP-ribose) (pADPr), a post-translational modification involved in several important biological processes, namely surveillance of genome integrity, cell cycle progression, initiation of the DNA damage response, apoptosis, and regulation of transcription. Poly(ADP-ribose) glycohydrolase (PARG), on the other hand, catabolizes pADPr and thereby accounts for the transient nature of poly(ADP-ribosyl)ation. Our investigation of the interactomes of PARP-1, PARP-2, and PARG by affinity-purification mass spectrometry (AP-MS) aimed, on the one hand, to confirm current knowledge on these interactomes and, on the other hand, to discover new protein partners which could offer insights into PARPs and PARG functions.</p> <p>Results</p> <p>PARP-1, PARP-2, and PARG were immunoprecipitated from human cells, and pulled-down proteins were separated by gel electrophoresis prior to in-gel trypsin digestion. Peptides were identified by tandem mass spectrometry. Our AP-MS experiments resulted in the identifications of 179 interactions, 139 of which are novel interactions. Gene Ontology analysis of the identified protein interactors points to five biological processes in which PARP-1, PARP-2 and PARG may be involved: RNA metabolism for PARP-1, PARP-2 and PARG; DNA repair and apoptosis for PARP-1 and PARP-2; and glycolysis and cell cycle for PARP-1.</p> <p>Conclusions</p> <p>This study reveals several novel protein partners for PARP-1, PARP-2 and PARG. It provides a global view of the interactomes of these proteins as well as a roadmap to establish the systems biology of poly(ADP-ribose) metabolism.</p

PARPs database: A LIMS systems for protein-protein interaction data mining or laboratory information management system

<p>Abstract</p> <p>Background</p> <p>In the "post-genome" era, mass spectrometry (MS) has become an important method for the analysis of proteins and the rapid advancement of this technique, in combination with other proteomics methods, results in an increasing amount of proteome data. This data must be archived and analysed using specialized bioinformatics tools.</p> <p>Description</p> <p>We herein describe "PARPs database," a data analysis and management pipeline for liquid chromatography tandem mass spectrometry (LC-MS/MS) proteomics. PARPs database is a web-based tool whose features include experiment annotation, protein database searching, protein sequence management, as well as data-mining of the peptides and proteins identified.</p> <p>Conclusion</p> <p>Using this pipeline, we have successfully identified several interactions of biological significance between PARP-1 and other proteins, namely RFC-1, 2, 3, 4 and 5.</p

Improvement in the molecular diagnosis of Machado-Joseph disease

Abstract BACKGROUND: Direct detection of the gene mutation allows for the confirmation of the clinical diagnosis of Machado-Joseph disease (MJD), the most frequent cause of autosomal dominant spinocerebellar ataxia worldwide. OBJECTIVE: To address the main difficulties in our national MJD predictive testing program. The first was the emergence of intermediate alleles, for which it is not yet possible to determine whether they will cause disease. The second was the issue of homoallelism, ie, homozygosity for 2 normal alleles with exactly the same (CAG)(n) length, which occurs in about 10% of all test results. METHODS: A large pedigree with 1 affected patient carrying a 71 and a 51 CAG repeat and 2 asymptomatic relatives carrying the 51 CAG repeat and normal-size alleles underwent clinical and molecular studies. Intragenic haplotypes for these alleles were determined. A representative sample of the healthy population in the region was obtained to assess the distribution of the normal (CAG)(n) length. We established the genotype for 4 intragenic polymorphisms in the gene for MJD (MJD1) in 21 homoallelic individuals, to distinguish their 2 normal chromosomes. In addition, we developed a new Southern blot method to completely exclude cases of nonamplification of expanded alleles in the homoallelic individuals. RESULTS: The study of the family in which the 51 CAG repeat was found suggests that the allele is apparently not associated with disease. These intermediate alleles were not present in a large sample of the healthy population from the same region. Intragenic polymorphisms allowed distinction of the 2 different normal alleles in all cases of homoallelism. The absence of an expanded allele was also confirmed by Southern blot. CONCLUSIONS: We propose an improved protocol for molecular testing for MJD. These strategies, developed to overcome the practical difficulties mostly in the presymptomatic and prenatal diagnosis of MJD, should prove useful for other polyglutamine-related disorders

Detection of antihydrogen annihilations with a Si-micro-strip and pure CsI detector

In 2002, the ATHENA collaboration reported the creation and detection of cold (~15 K) antihydrogen atoms [1]. The observation was based on the complete reconstruction of antihydrogen annihilations, simultaneous and spatially correlated annihilations of an antiproton and a positron. Annihilation byproducts are measured with a cylindrically symmetric detector system consisting of two layers of double sided Si-micro-strip modules that are surrounded by 16 rows of 12 pure CsI crystals (13 x 17.5 x 17 mm^3). This paper gives a brief overview of the experiment, the detector system, and event reconstruction. Reference 1. M. Amoretti et al., Nature 419, 456 (2002).Comment: 7 pages, 5 figures; Proceedings for the 8th ICATPP Conference on Astroparticle, Particle, Space Physics, Detectors and Medical Physics Applications (Como, Italy October 2003) to be published by World Scientific (style file included