An Ecological Risk Assessment of Hexachlorobutadiene

Hexachlorobutadiene (HCBD) has never been commercially produced in Canada and was imported in the past for use as a solvent. Anthropogenic activity is linked with the entry of this substance into the environment. While current Canadian sources of HCBD involve low-level releases, potentially they can be numerous. Until recently, the most significant point source of HCBD in Canada appeared to be the Cole Drain, which discharges into the St. Clair River at Sarnia, Ontario, and includes outfalls from an industrial landfill and a few industrial companies. HCBD has been detected in Canadian surface waters, sediments, aquatic organisms and, occasionally, air. Considering the properties of the substance, including its persistence and bioaccumulation characteristics, the environmental risk assessment of HCBD was focused on the aquatic environment. The results of a conservative assessment suggest that there is a risk of harmful effects for benthic organisms exposed to sediments contaminated by HCBD in the most contaminated part of the St. Clair River.     

Functional Diversity of Carbohydrate-Active Enzymes Enabling a Bacterium to Ferment Plant Biomass

Microbial metabolism of plant polysaccharides is an important part of environmental carbon cycling, human nutrition, and industrial processes based on cellulosic bioconversion. Here we demonstrate a broadly applicable method to analyze how microbes catabolize plant polysaccharides that integrates carbohydrate-active enzyme (CAZyme) assays, RNA sequencing (RNA-seq), and anaerobic growth screening. We apply this method to study how the bacterium Clostridium phytofermentans ferments plant biomass components including glucans, mannans, xylans, galactans, pectins, and arabinans. These polysaccharides are fermented with variable efficiencies, and diauxies prioritize metabolism of preferred substrates. Strand-specific RNA-seq reveals how this bacterium responds to polysaccharides by up-regulating specific groups of CAZymes, transporters, and enzymes to metabolize the constituent sugars. Fifty-six up-regulated CAZymes were purified, and their activities show most polysaccharides are degraded by multiple enzymes, often from the same family, but with divergent rates, specificities, and cellular localizations. CAZymes were then tested in combination to identify synergies between enzymes acting on the same substrate with different catalytic mechanisms. We discuss how these results advance our understanding of how microbes degrade and metabolize plant biomass.     

A Tissue-Level Electromechanical Model of the Left Ventricle: Application to the Analysis of Intraventricular Pressure

The ventricular pressure profile is characteristic of the cardiac contraction progress and is useful to evaluate the cardiac performance. In this contribution, a tissue-level electromechanical model of the left ventricle is proposed, to assist the interpretation of left ventricular pressure waveforms. The left ventricle has been modeled as an ellipsoid composed of twelve mechano-hydraulic sub-systems. The asynchronous contraction of these twelve myocardial segments has been represented in order to reproduce a realistic pressure profiles. To take into account the different energy domains involved, the tissue-level scale and to facilitate the building of a modular model, multiple formalisms have been used: Bond Graph formalism for the mechano-hydraulic aspects and cellular automata for the electrical activation. An experimental protocol has been defined to acquire ventricular pressure signals from three pigs, with different afterload conditions. Evolutionary Algorithms have been used to identify the model parameters in order to minimize the error between experimental and simulated ventricular pressure signals. Simulation results show that the model is able to reproduce experimental ventricular pressure. In addition, electro-mechanical activation times have been determined in the identification process. For example, the maximum electrical activation time is reached, respectively, 96.5, 139.3 and 131.5 ms for the first, second, and third pigs. These preliminary results are encouraging for the application of the model on non-invasive data like ECG, arterial pressure or myocardial strain.     

Negatively charged self-assembling DNA/poloxamine nanospheres for in vivo gene transfer

Over the past decade, numerous nonviral cationic vectors have been synthesized. They share a high density of positive charges and efficiency for gene transfer in vitro. However, their positively charged surface causes instability in body fluids and cytotoxicity, thereby limiting their efficacy in vivo. Therefore, there is a need for developing alternative molecular structures. We have examined tetrabranched amphiphilic block copolymers consisting of four polyethyleneoxide/polypropyleneoxide blocks centered on an ethylenediamine moiety. Cryo-electron microscopy, ethidium bromide fluorescence and light and X-ray scattering experiments performed on vector–DNA complexes showed that the dense core of the nanosphere consisted of condensed DNA interacting with poloxamine molecules through electrostatic, hydrogen bonding and hydrophobic interactions, with DNA molecules also being exposed at the surface. The supramolecular organization of block copolymer/DNA nanospheres induced the formation of negatively charged particles. These particles were stable in a solution that had a physiological ionic composition and were resistant to decomplexation by heparin. The new nanostructured material, the structure of which clearly contrasted with that of lipoplexes and polyplexes, efficiently transferred reporter and therapeutic genes in skeletal and heart muscle in vivo. Negatively charged supramolecular assemblies hold promise as therapeutic gene carriers for skeletal and heart muscle-related diseases and expression of therapeutic proteins for local or systemic uses.     

Factors associated with the 6-minute walk distance in patients with systemic sclerosis

Background

There is an ongoing debate regarding the relevance of the 6-minute walking distance (6MWD) in systemic sclerosis (SSc) assessment, widely used as a usual test in these patients as well as an outcome measure in clinical trials. In this work, we aimed to assess the associations between the 6MWD and various disease parameters in patients with SSc.

Methods

Consecutive patients followed in our SSc National Reference Centre were included in this cross-sectional study if they fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc. Data were systematically collected during a comprehensive standardized evaluation that included a 6-minute walk test, clinical assessment, biological results, pulmonary function tests, transthoracic echocardiography, composite scores (European Scleroderma Study Group Activity Index, Medsger severity score, Health Assessment Questionnaire–Disability Index (HAQ-DI)) and treatments.Associations of the 6MWD with various disease parameters were assessed by linear regression in univariate and multivariate analyses.

Results

The study population comprised 298 patients (females 81%; mean age 58.2?±?13.3 years; limited cutaneous SSc 82%; interstitial lung disease (ILD) 42%; pulmonary arterial hypertension (PAH) 6%). The 6MWD was significantly and independently associated with gender, age, body mass index, baseline heart rate (HR), HR variation during the test, PAH, history of arterial thrombosis and C-reactive protein levels, as well as with the HAQ-DI score in a sensitivity analysis. Muscle involvement, joint involvement and ILD were not independently associated with the 6MWD.

Conclusions

During SSc, the 6MWD is independently associated with initial HR and HR variation; with PAH but not ILD, suggesting that pulmonary vasculopathy may have a greater impact than parenchymal involvement on functional limitation; and with global markers of disease activity and patient disability. These results give clinicians further insight into how to interpret the 6MWD in the context of SSc.

     

Marking hard-shelled gastropods: tag loss, impact on life-history traits, and perspectives in biology

Abstract. Individual marking has long been used in many fields of biology. However, capture–mark–recapture (CMR) studies are not evenly distributed among taxonomic groups, with most studies focusing on vertebrates. For example, a limited number of studies have been conducted in gastropods, in sharp contrast to their important role as biological models or exploited natural resources. The lack of standard, validated marking techniques certainly contributes to the limited use of CMR. In this article, we evaluate two fundamental requirements for a marking technique to be suitable, i.e., tag loss (two experiments) and impact on life-history traits (survival, growth, and fecundity, in three experiments). Five marking techniques for hard-shelled gastropods were tested in the freshwater snail Physa acuta (Pulmonata). The tag-loss rate per month was lower for glued plastic marks (0.01) than for paint marks (0.03–0.07), and the tag-loss rate varied among colors (gouache paint). Under laboratory conditions, the life-history traits were not significantly affected by marking. We thus recommend using glued plastic marks for long-term studies, and paint marks for mass marking, with double marking to account for tag-loss rate. Based on an extensive literature survey, we also review current CMR practices in gastropod studies and suggest general improvements that would prove useful in both this group and invertebrates in general.     

Hepatitis B virus subviral envelope particle morphogenesis and intracellular trafficking

Hepatitis B virus (HBV) is unusual in that its surface proteins (small [S], medium, and large [L]) are not only incorporated into the virion envelope but they also bud into empty subviral particles in great excess over virions. The morphogenesis of these subviral envelope particles remains unclear, but the S protein is essential and sufficient for budding. We show here that, in contrast to the presumed model, the HBV subviral particle formed by the S protein self-assembles into branched filaments in the lumen of the endoplasmic reticulum (ER). These long filaments are then folded and bridged for packing into crystal-like structures, which are then transported by ER-derived vesicles to the ER-Golgi intermediate compartment (ERGIC). Within the ERGIC, they are unpacked and relaxed, and their size and shape probably limits further progression through the secretory pathway. Such progression requires their conversion into spherical particles, which occurred spontaneously during the purification of these filaments by affinity chromatography. Small branched filaments are also formed by the L protein in the ER lumen, but these filaments are not packed into transport vesicles. They are transported less efficiently to the ERGIC, potentially accounting for the retention of the L protein within cells. These findings shed light on an important step in the HBV infectious cycle, as the intracellular accumulation of HBV subviral filaments may be directly linked to viral pathogenesis.