McMaster University

About: McMaster University is a education organization based out in Hamilton, Ontario, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 41361 authors who have published 101269 publications receiving 4251422 citations.

Biotic Ligand Model, a Flexible Tool for Developing Site-Specific Water Quality Guidelines for Metals

Abstract: The biotic ligand model (BLM) is a mechanistic approach that greatly improves our ability to generate site-specific ambient water quality criteria (AWQC)for metals in the natural environment relative to conventional relationships based only on hardness. The model is flexible; all aspects of water chemistry that affect toxicity can be included, so the BLM integrates the concept of bioavailability into AWQC--in essence the computational equivalent of water effect ratio (WER) testing. The theory of the BLM evolved from the gill surface interaction model (GSIM) and the free ion activity model (FIAM). Using an equilibrium geochemical modeling framework, the BLM incorporates the competition of the free metal ion with other naturally occurring cations (e.g., Ca2+, Na+, Mg2-, H+), togetherwith complexation by abiotic ligands [e.g., DOM (dissolved organic matter), chloride, carbonates, sulfide] for binding with the biotic ligand, the site of toxic action on the organism. On the basis of fish gill research, the biotic ligands appear to be active ion uptake pathways (e.g., Na+ transporters for copper and silver, Ca2+ transporters for zinc, cadmium, lead, and cobalt), whose geochemical characteristics (affinity = log K, capacity = Bmax) can be quantified in short-term (3-24 h) in vivo gill binding tests. In general, the greater the toxicity of a particular metal, the higher the log K. The BLM quantitatively relates short-term binding to acute toxicity, with the LA50 (lethal accumulation) being predictive of the LC50 (generally 96 h for fish, 48 h for daphnids). We critically evaluate currently available BLMs for copper, silver, zinc, and nickel and gill binding approaches for cadmium, lead, and cobalt on which BLMs could be based. Most BLMs originate from tests with fish and have been recalibrated for more sensitive daphnids by adjustment of LA50 so as to fit the results of toxicity testing. Issues of concern include the arbitrary nature of LA50 adjustments; possible mechanistic differences between daphnids and fish that may alter log K values, particularly for hardness cations (Ca2+, Mg2+); assumption of fixed biotic ligand characteristics in the face of evidence that they may change in response to acclimation and diet; difficulties in dealing with DOM and incorporating its heterogeneity into the modeling framework; and the paucity of validation exercises on natural water data sets. Important needs include characterization of biotic ligand properties at the molecular level; development of in vitro BLMs, extension of the BLM approach to a wider range of organisms, to the estuarine and marine environment, and to deal with metal mixtures; and further development of BLM frameworks to predict chronic toxicity and thereby generate chronic AWQC.

Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

Abstract: We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.