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The molecular composition of dissolved organic matter (DOM) is increasingly recognized as fundamentally important to mercury transport and transformations, with numerous approaches undertaken to examine DOM characteristics beyond dissolved organic carbon concentrations. In this study, we use a high-resolution mass spectrometry approach, Fourier-transform ion cyclotron resonance mass spectrometry, to characterize DOM compound classes, DOM aromaticity (AImod), and the nominal oxygenation state of carbon (NOSC) across thirteen small boreal forest streams in central Canada. We then relate the relative abundance of hundreds of different DOM molecules with inorganic mercury and methylmercury (MeHg) concentrations across late spring and fall seasons. The number of significant correlations and the classes of DOM compounds significantly correlating with inorganic mercury and MeHg concentrations differs substantially across seasons and between mercury forms. For inorganic mercury, the abundance of nitrogen and sulfur containing DOM are most often positively correlated (mean ρ = 0.80) in the late spring, whereas during the fall, the abundance of low-oxidized lignins is more important, though with weaker correlations (mean ρ = 0.51). For MeHg, low-oxidized lignins and hydrolysable tannins, likely sourced from conifer throughfall and litter, account for up to 83% of all DOM-MeHg correlations regardless of season. Further network analyses reveal that the strongest and most significant inorganic mercury-DOM correlations are found across a wide range of NOSC values, indicating that DOM involved with the transport of inorganic mercury encompasses a wide range of polarities and thermodynamic stabilities. In contrast, DOM molecules exclusively correlated with MeHg concentrations have more positive NOSC and AImod values, implying the preferential transport of MeHg with more thermodynamically stable and aromatic DOM molecules. DOM molecules significantly correlated with both inorganic mercury and MeHg concentrations are found exclusively in the late spring. Overall, this non-targeted approach may help to inform further targeted investigations, especially as it relates to the underrepresented importance of plant biomolecules in facilitating mercury transport. [ABSTRACT FROM AUTHOR]

Bacterial wilt caused byCurtobacterium flaccumfacienspv.flaccumfaciensis an important new disease of common bean (Phaseolus vulgaris) in western Canada. Both yellow and orange variants of the pathogen were found in the region. A controlled environment study was conducted to assess 124 common bean cultivars and lines from eight market classes for resistance to the yellow and orange variants of the pathogen, using the hilum injury/seed inoculation method. Results of the screening tests showed significant (P < 0.05) differences in resistance to bacterial wilt among the cultivars or lines. The great northern line L02E317, the great northern cultivar Resolute and pinto lines L02B662 and 999S-2A, were highly resistant to both variants of the pathogen, with disease severity indices of 0 on a rating scale of 0 (no wilt symptoms) to 5 (dead seedling). Resistant cultivars or lines were found among black, great northern, pink, pinto, small red and Flor de Mayo bean market classes. The study concludes that new bacterial wilt-resistant germplasm exists among Canadian bean cultivars and lines, and constitutes a valuable resource for breeding common beans for resistance to both yellow and orange variants ofC. flaccumfacienspv.flaccumfaciens. [ABSTRACT FROM AUTHOR]

When sclerotia of a Canadian isolate of Sclerotinia sclerotiorum were exposed to temperatures of -10 or -20°C for 4 weeks, their germination behaviour changed from carposenic to myceliogenic type. Mycelial growth from sclerotia exposed to -20°C was more vigorous than that from sclerotia exposed to -10°C. The mode of germination in sclerotia treated with above-freezing temperatures of 0.5, 10, 15, 25 or 30°C did not change: they retained the capacity for carpogenic germination. The possible epidemiological impact of this low-temperature induction or myceliogenic germination on lee development of sclerotinia wilt of sunflower seedlings in western Canada is discussed. [ABSTRACT FROM AUTHOR]

Aim: To compare the accuracy and repeatability for the assessment of axial spondyloarthritis (axSpA) between single T2-weighted (W) Dixon and the standard protocol (T1W and fat-suppressed T2W sequence).Materials and Methods: One hundred and seven patients were diagnosed based on the Assessment in SpondyloArthritis International Society (ASAS) criteria by rheumatologists. Two radiologists reviewed two protocols separately. Positive MRI, active sacroiliitis, chronic sacroiliitis, Spondyloarthritis Research Consortium of Canada (SPARCC) scores, and Sacroiliac Joint (SIJ) Structural Score (SSS) scores were recorded. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of bone marrow oedema (BME) and fat deposition were measured.Results: No significant difference in diagnostic performance was observed between T2W Dixon sequence and the standard protocol (all p>0.05). Diagnostic performance of positive MRI was not significant difference between the T2W Dixon sequence and the standard protocol (area under the curve [AUC], 0.73-0.75 versus 0.74-0.76). Cohen's kappa coefficients and intraclass correlation coefficients (ICCs) showed similar intra-observer and interobserver agreements. Of note, interobserver agreements of BME and fat metaplasia on the T2W Dixon sequence were slightly higher than the standard protocol. SNRs and CNRs were significantly higher on the T2W Dixon than the standard protocol (all p≤0.05).Conclusion: The single T2W Dixon sequence may replace the standard protocol in patients with suspected axSpA and shorten the acquisition time. [ABSTRACT FROM AUTHOR]

This article presents information on the registration of Resolute great northern bean. Resolute, an early-maturing upright great northern common bean, was developed at the Agriculture and Agri-Food Canada (AAFC) Research Centre in Lethbridge, Alberta in collaboration with the AAFC Research Station in Morden, Manitoba and released in 2004. Resolute was tested in the narrow-row dry bean registration trials in Alberta, Saskatchewan and Manitoba for 4 yr and registered in 2004. It is resistant to both yellow and orange strains of the bacterial wilt pathogen. Resolute is particularly well adapted to narrow row production. Line L98E212 was tested in the official Canadian prairie Bean Cooperative Registration Trials-Narrow Rows from 2000 to 2003, at 23 station-years. Plants from pods collected in Vauxhall, Alberta in 2003, were grown in progeny-rows in Chile in 2003 to 2004. Resolute is resistant to both the yellow and orange strains of bacterial wilt, while the check, US1140 is susceptible, with a DST of 1.65 for the yellow strain and 1.95 for the orange strain.

Background: This study leverages a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between 1,400 metabolites and pulmonary fibrosis, using genetic variation as instrumental variables. By adhering to stringent criteria for instrumental variable selection, the research aims to uncover metabolic pathways that may influence the risk and progression of pulmonary fibrosis, providing insights into potential therapeutic targets., Methods: Utilizing data from the OpenGWAS project, which includes a significant European cohort, and metabolite GWAS data from the Canadian Longitudinal Aging Study (CLSA), the study employs advanced statistical methods. These include inverse variance weighting (IVW), weighted median estimations, and comprehensive sensitivity analyses conducted using the R software environment to ensure the robustness of the causal inferences., Results: The study identified 62 metabolites with significant causal relationships with pulmonary fibrosis, highlighting both risk-enhancing and protective metabolic factors. This extensive list of metabolites presents a broad spectrum of potential therapeutic targets and biomarkers for early detection, underscoring the metabolic complexity underlying pulmonary fibrosis., Conclusions: The findings from this MR study significantly advance our understanding of the metabolic underpinnings of pulmonary fibrosis, suggesting that alterations in specific metabolites could influence the risk and progression of the disease. These insights pave the way for the development of novel diagnostic and therapeutic strategies, emphasizing the potential of metabolic modulation in managing pulmonary fibrosis., (© 2024. The Author(s).)

Terrestrial ecosystems store large amounts of mercury (Hg), which may be subject to methylation, mobilization and uptake into downstream aquatic ecosystems. Mercury concentrations, methylation and demethylation potentials are not well characterized simultaneously across different habitats in boreal forest ecosystems, particularly not so in stream sediment, leading to uncertainties about the importance of various habitats as primary production areas of the bioaccumulative neurotoxin methylmercury (MeHg). In this study, we collected soil and sediment samples from 17 undisturbed, central Canadian boreal forested watersheds during spring, summer and fall to robustly characterize the spatial (upland and riparian/wetland soils, and stream sediment) and seasonal patterns of total Hg (THg) and MeHg concentrations. Mercury methylation and MeHg demethylation potentials (K meth and K demeth ) in the soils and sediment were also assessed using enriched stable Hg isotope assays. We found the highest K meth and %-MeHg in stream sediment. In both riparian and wetland soils, Hg methylation was lower and less seasonally variable compared to stream sediment, but had comparable MeHg concentrations, suggesting longer-term storage of MeHg produced in these soils. Soil and sediment carbon content, and THg and MeHg concentrations were strong covariates across habitats. Additionally, sediment carbon content was important for delineating between stream sediment with relatively high vs. relatively low Hg methylation potential, which generally separated between different landscape physiographies. Broadly, this large and spatiotemporally diverse dataset is an important baseline for understanding Hg biogeochemistry in boreal forests both in Canada and possibly in many other boreal systems globally. This work is particularly important with respect to future possible impacts from natural and anthropogenic perturbations, which are increasingly straining boreal ecosystems in various parts of the world., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Interactions between genes and early-life exposures during conception, fetal life, infancy, and early childhood have been shown to affect an individual's health later in life. Maternal undernutrition and obesity, gestational diabetes, and impaired growth in utero and in early life are associated with adiposity and overweight and obesity in childhood, which are risk factors for poor health trajectories and non-communicable diseases. In Canada, China, India, and South Africa, 10-30% of children aged 5-16 years are overweight or obese., Methods: The application of developmental origins of health and disease principles offers a novel approach to prevention of overweight and obesity and reduction of adiposity by delivering integrated interventions across the life course, starting before conception and continuing through early childhood. The Healthy Life Trajectories Initiative (HeLTI) was established in 2017 through a unique collaboration between national funding agencies in Canada, China, India, South Africa, and WHO. The aim of HeLTI is to evaluate the effect of an integrated four-phase intervention starting preconceptionally and continuing through pregnancy, infancy, and early childhood on reducing childhood adiposity (fat mass index) and overweight and obesity, and optimising early child development, nutrition, and other healthy behaviours., Findings: Approximately 22 000 women are being recruited in Shanghai (China), Mysore (India), Soweto (South Africa), and across various provinces of Canada. Women who conceive (an expected 10 000) and their children will be followed up until the child reaches the age of 5 years., Interpretation: HeLTI has harmonised the intervention, measures, tools, biospecimen collection, and analysis plans for the trial to be run across four countries. HeLTI will help establish whether an intervention aimed at addressing maternal health behaviours, nutrition, and weight; providing psychosocial support to reduce maternal stress and prevent mental illness; optimising infant nutrition, physical activity, and sleep; and promoting parenting skills can reduce the intergenerational risk of excess childhood adiposity and overweight and obesity across diverse settings., Funding: Canadian Institutes of Health Research; National Science Foundation of China; Department of Biotechnology, India; and South African Medical Research Council., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs)., Methods: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response., Results: Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n = 197), common adverse events (≥ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade ≥ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively., Conclusion: Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study., Competing Interests: Lihua E. BuddeConsulting or Advisory Role: Roche/Genentech, Kite/Gilead, Novartis, BeiGeneResearch Funding: Merck, Amgen, MustangBio, AstraZenecaPatents, Royalties, Other Intellectual Property: CCR4 CAR T cells for treatment of patients with CCR4-positive cancer. CD33CAR for treatment of patients with CD33+ acute myeloid leukemiaTravel, Accommodations, Expenses: Roche/Genentech, Kite/Gilead, AstraZeneca Sarit AssoulineStock and Other Ownership Interests: Knight PharmaceuticalsHonoraria: Janssen Oncology, Pfizer, AbbVie, Novartis Canada Pharmaceuticals Inc, AstraZeneca, BMSConsulting or Advisory Role: Roche/Genentech, BeiGeneResearch Funding: Roche Canada (Inst), Takeda (Inst), Astex Pharmaceuticals (Inst), BeiGene (Inst), Novartis (Inst)Travel, Accommodations, Expenses: Roche Canada Laurie H. SehnHonoraria: Amgen, Apobiologix, AbbVie, Celgene, Gilead Sciences, Janssen-Ortho, Karyopharm Therapeutics, Kite, a Gilead company, Lundbeck, Merck, Roche/Genentech, Seattle Genetics, Takeda, Teva, TG Therapeutics, AstraZeneca, Acerta Pharma, morphosys, Incyte, Debiopharm Group, Sandoz-Novartis, Verastem, GenmabConsulting or Advisory Role: Celgene, AbbVie, Seattle Genetics, TG Therapeutics, Janssen, Amgen, Roche/Genentech, Gilead Sciences, Lundbeck, Amgen, apobiologix, Karyopharm Therapeutics, Kite, a Gilead company, Merck, Takeda, Teva, TG therapeutics, AstraZeneca, Acerta Pharma, MorphoSys, Incyte, Debiopharm Group, Sandoz-Novartis, Genmab, VerastemResearch Funding: Roche/Genentech (Inst), Teva (Inst) Stephen J. SchusterConsulting or Advisory Role: Celgene, Nordic Nanovector, Novartis, AbbVie, Acerta Pharma/AstraZeneca, Alimera Sciences, BeiGene, Juno Therapeutics, Loxo Oncology, Tessa Therapeutics, Genentech/RocheResearch Funding: Novartis (Inst), Pharmacyclics (Inst), Adaptive Biotechnologies (Inst), Merck (Inst), Genentech/Roche (Inst), Celgene (Inst), Juno Therapeutics (Inst), AbbVie (Inst), Incyte (Inst), TG Therapeutics (Inst), DTRM (Inst)Patents, Royalties, Other Intellectual Property: Patent Combination Therapies of CAR and PD-1 Inhibitors (via University of Pennsylvania with royalties to Novartis) Sung-Soo YoonHonoraria: NovartisConsulting or Advisory Role: Janssen, Takeda, Amgen, Celgene/JazzResearch Funding: Kyowa Kirin, Roche/Genentech, Yuhan Dok Hyun YoonHonoraria: Celltrion, Roche, Janssen, Amgen, Celgene, Samyang, Kirin Pharmaceuticals, TakedaConsulting or Advisory Role: Roche, Janssen, Amgen, Celgene, Green Cross, NovartisResearch Funding: Samyang, Abclone, Roche/Genentech, Janssen Oncology, Amgen, Genmab, Boryung, Eutilex Matthew J. MatasarStock and Other Ownership Interests: MerckHonoraria: Genentech, Roche, Bayer, Pharmacyclics, Seattle Genetics, Takeda, Immunovaccine, ADC Therapeutics, Karyopharm TherapeuticsConsulting or Advisory Role: Genentech, Bayer, Merck, Juno Therapeutics, Roche, Teva, Rocket Medical, Seattle Genetics, Daiichi Sankyo, TakedaResearch Funding: Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Rocket Medical, Seattle Genetics, Immunovaccine, IGM Biosciences , IGM BiosciencesTravel, Accommodations, Expenses: Genentech, Roche, Seattle Genetics, Bayer Francesc BoschConsulting or Advisory Role: AstraZeneca, Roche/Genentech, Janssen-Cilag, Lilly, AbbVie, Kite, a Gilead company, BeiGene, NovartisSpeakers' Bureau: AbbVie, Janssen, Roche, AstraZenecaResearch Funding: Janssen, AstraZeneca Loretta J. NastoupilHonoraria: Celgene, Gilead Sciences, Novartis, Bayer, Janssen Oncology, Pfizer, Gamida Cell, TG Therapeutics, Bristol Myers Squibb, ADC Therapeutics, Morphosys, Epizyme, GenmabResearch Funding: TG Therapeutics, Janssen Biotech, Celgene, Genentech/Roche, LAM Therapeutics, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Ian W. FlinnConsulting or Advisory Role: AbbVie (Inst), Seattle Genetics (Inst), TG Therapeutics (Inst), Verastem (Inst), Roche (Inst), Gilead Sciences (Inst), Kite, a Gilead company (Inst), Janssen (Inst), BeiGene (Inst), Takeda (Inst), AstraZeneca (Inst), Juno Therapeutics (Inst), Unum Therapeutics (Inst), MorphoSys (Inst), Nurix (Inst), Shanghai Yingli Pharmaceuticals (Inst), Genentech (Inst), Great Point Partners (Inst), Iksuda Therapeutics (Inst), Novartis (Inst), Pharmacyclics (Inst), Century Therapeutics (Inst), Hutchison MediPharma (Inst), SERVIER (Inst), Vincerx Pharma (Inst), Genmab (Inst), InnoCare Pharma (Inst)Research Funding: Acerta Pharma (Inst), Agios (Inst), Calithera Biosciences (Inst), Celgene (Inst), Constellation Pharmaceuticals (Inst), Genentech (Inst), Gilead Sciences (Inst), Incyte (Inst), Infinity Pharmaceuticals (Inst), Janssen (Inst), Karyopharm Therapeutics (Inst), Kite, a Gilead company (Inst), Novartis (Inst), Pharmacyclics (Inst), Portola Pharmaceuticals (Inst), Roche (Inst), TG Therapeutics (Inst), Trillium Therapeutics (Inst), AbbVie (Inst), ArQule (Inst), BeiGene (Inst), Curis (Inst), FORMA Therapeutics (Inst), Forty Seven (Inst), Merck (Inst), Pfizer (Inst), Takeda (Inst), Teva (Inst), Verastem (Inst), AstraZeneca (Inst), Juno Therapeutics (Inst), Unum Therapeutics (Inst), MorphoSys (Inst), Seattle Genetics (Inst), IGM Biosciences (Inst), Loxo (Inst), Rhizen Pharmaceuticals (Inst), Triact Therapeutics (Inst) Mazyar ShadmanConsulting or Advisory Role: AbbVie, Genentech, AstraZeneca, Sound Biologics, Cellectar, Pharmacyclics, BeiGene, Bristol Myers Squibb/Celgene, MorphoSys, Innate Pharma, Kite, a Gilead company, Adaptive Biotechnologies, EpizymeResearch Funding: Pharmacyclics (Inst), Acerta Pharma (Inst), Merck (Inst), TG Therapeutics (Inst), BeiGene (Inst), Celgene (Inst), Genentech (Inst), MustangBio (Inst), AbbVie (Inst), Sunesis Pharmaceuticals (Inst), Bristol Myers Squibb/Celgene Catherine DiefenbachStock and Other Ownership Interests: Gilead SciencesConsulting or Advisory Role: Seattle Genetics, Bayer, Bristol Myers Squibb, Genentech/Roche, Merck, Janssen, Celgene, MorphoSysResearch Funding: Seattle Genetics (Inst), Genentech (Inst), Incyte (Inst), LAM Therapeutics (Inst), Merck (Inst), Bristol Myers Squibb (Inst), Millennium (Inst), Roche/Genentech (Inst), Janssen (Inst), MEI Pharma (Inst), Trillium Therapeutics (Inst), Astex Pharmaceuticals (Inst)Expert Testimony: Jim Harmon Carol O'HearEmployment: Genentech/RocheStock and Other Ownership Interests: Genentech/RochePatents, Royalties, Other Intellectual Property: Antibody bufferingTravel, Accommodations, Expenses: Genentech/Roche Huang HuangEmployment: Roche Canada Antonia KwanEmployment: Genentech/RocheStock and Other Ownership Interests: Roche/Genentech Chi-Chung LiEmployment: Roche/GenentechStock and Other Ownership Interests: Roche/GenentechPatents, Royalties, Other Intellectual Property: Patent applications pertaining to the development and dosing of bispecific antibodies Emily C. PiccioneEmployment: GenentechStock and Other Ownership Interests: Roche/Genentech Michael C. WeiEmployment: Genentech/RocheStock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Genentech/Roche Shen YinEmployment: GenentechStock and Other Ownership Interests: GenentechTravel, Accommodations, Expenses: Genentech Nancy L. BartlettConsulting or Advisory Role: Seattle Genetics, Roche/Genentech, ADC Therapeutics, BTG, Acerta PharmaResearch Funding: Seattle Genetics (Inst), Kite, a Gilead company (Inst), Merck (Inst), Bristol Myers Squibb (Inst), Celgene (Inst), Immune Design (Inst), Forty Seven (Inst), Janssen (Inst), Pharmacyclics (Inst), Millennium (Inst), ADC Therapeutics (Inst), Autolus (Inst), Roche/Genentech (Inst), Pfizer (Inst), Affimed Therapeutics (Inst)No other potential conflicts of interest were reported.

Background: Diabetes Mellitus is an increasingly prevalent chronic disease characterized by the body's inability to metabolize glucose. The objective of this study was to build an effective predictive model with high sensitivity and selectivity to better identify Canadian patients at risk of having Diabetes Mellitus based on patient demographic data and the laboratory results during their visits to medical facilities., Methods: Using the most recent records of 13,309 Canadian patients aged between 18 and 90 years, along with their laboratory information (age, sex, fasting blood glucose, body mass index, high-density lipoprotein, triglycerides, blood pressure, and low-density lipoprotein), we built predictive models using Logistic Regression and Gradient Boosting Machine (GBM) techniques. The area under the receiver operating characteristic curve (AROC) was used to evaluate the discriminatory capability of these models. We used the adjusted threshold method and the class weight method to improve sensitivity - the proportion of Diabetes Mellitus patients correctly predicted by the model. We also compared these models to other learning machine techniques such as Decision Tree and Random Forest., Results: The AROC for the proposed GBM model is 84.7% with a sensitivity of 71.6% and the AROC for the proposed Logistic Regression model is 84.0% with a sensitivity of 73.4%. The GBM and Logistic Regression models perform better than the Random Forest and Decision Tree models., Conclusions: The ability of our model to predict patients with Diabetes using some commonly used lab results is high with satisfactory sensitivity. These models can be built into an online computer program to help physicians in predicting patients with future occurrence of diabetes and providing necessary preventive interventions. The model is developed and validated on the Canadian population which is more specific and powerful to apply on Canadian patients than existing models developed from US or other populations. Fasting blood glucose, body mass index, high-density lipoprotein, and triglycerides were the most important predictors in these models.

The use of treated municipal wastewater residues (biosolids) as fertilizers is an attractive, inexpensive option for growers and farmers. Various regulatory bodies typically employ indicator organisms (fecal coliforms, E. coli and Salmonella) to assess the adequacy and efficiency of the wastewater treatment process in reducing pathogen loads in the final product. Molecular detection approaches can offer some advantages over culture-based methods as they can simultaneously detect a wider microbial species range, including non-cultivable microorganisms. However, they cannot directly assess the viability of the pathogens. Here, we used bacterial enumeration methods together with molecular methods including qPCR, 16S rRNA and cpn60 gene amplicon sequencing and shotgun metagenomic sequencing to compare pre- and post-treatment biosolids from two Canadian wastewater treatment plants (WWTPs). Our results show that an anaerobic digestion WWTP was unsuccessful at reducing the live indicator organism load (coliforms, generic E. coli and Salmonella) below acceptable regulatory criteria, while biosolids from a dewatering/pelletization WWTP met these criteria. DNA from other pathogens was detected by the molecular methods, but these species were considered less abundant. Clostridium DNA increased significantly following anaerobic digestion treatments. In addition to pathogen DNA, genes related to virulence and antibiotic resistance were identified in treated biosolids. Shotgun metagenomics revealed the widest range of pathogen DNA and, among the approaches used here, was the only approach that could access functional gene information in treated biosolids. Overall, our results highlight the potential usefulness of amplicon sequencing and shotgun metagenomics as complementary screening methods that could be used in parallel with culture-based methods, although more detailed comparisons across a wider range of sites would be needed.

Biodegradation of crude oil in subsurface petroleum reservoirs has adversely affected the majority of the world's oil, making recovery and refining of that oil more costly. The prevalent occurrence of biodegradation in shallow subsurface petroleum reservoirs has been attributed to aerobic bacterial hydrocarbon degradation stimulated by surface recharge of oxygen-bearing meteoric waters. This hypothesis is empirically supported by the likelihood of encountering biodegraded oils at higher levels of degradation in reservoirs near the surface. More recent findings, however, suggest that anaerobic degradation processes dominate subsurface sedimentary environments, despite slow reaction kinetics and uncertainty as to the actual degradation pathways occurring in oil reservoirs. Here we use laboratory experiments in microcosms monitoring the hydrocarbon composition of degraded oils and generated gases, together with the carbon isotopic compositions of gas and oil samples taken at wellheads and a Rayleigh isotope fractionation box model, to elucidate the probable mechanisms of hydrocarbon degradation in reservoirs. We find that crude-oil hydrocarbon degradation under methanogenic conditions in the laboratory mimics the characteristic sequential removal of compound classes seen in reservoir-degraded petroleum. The initial preferential removal of n-alkanes generates close to stoichiometric amounts of methane, principally by hydrogenotrophic methanogenesis. Our data imply a common methanogenic biodegradation mechanism in subsurface degraded oil reservoirs, resulting in consistent patterns of hydrocarbon alteration, and the common association of dry gas with severely degraded oils observed worldwide. Energy recovery from oilfields in the form of methane, based on accelerating natural methanogenic biodegradation, may offer a route to economic production of difficult-to-recover energy from oilfields.

The purpose of this study was to enhance the sensitivity of the Western blot (WB) test for use as an alternative and confirmatory method for the diagnosis of scrapie and chronic wasting disease (CWD) in Canada by comparing 2 sample preparation procedures: an abnormal prion protein (PrPSc) concentration procedure using sodium phosphotungstic acid (PTA) precipitation and a procedure using crude sample without precipitation. A total of 100 cerebrum samples (52 sheep and 48 elk), including 66 negative (31 sheep, 35 elk) and 34 positive (21 scrapie and 13 CWD positive) samples diagnosed by using immunohistochemistry (IHC) on retropharyngeal lymph node (RPLN) and medulla oblongata at obex, were tested by using WB with the 2 sample preparation procedures. The WB using non-PTA enriched sample (crude extract) detected, on average, only 71.7% (9 of 15, 60.0% for scrapie, 5 of 6, 83.3% for CWD) of the samples that tested positive by using WB with PTA enriched samples. No case was positive by WB using crude extract but negative by WB using PTA enriched sample. No false positive was found. Serial dilution of PTA precipitated samples demonstrated that the technique increases the detection limit approximately 100 fold. Additionally, the comparison of the WB and IHC on cerebrum from all the positive cases demonstrated that WB following PTA precipitation and IHC had 100% agreement by detecting 6 positive for CWD on cerebrum; while IHC detected scrapie in only 14 out of 15 positive cerebrum samples by using WB following PTA precipitation. Phosphotungstic acid precipitation is therefore a useful adjunct to WB analysis of scrapie and CWD and tissues.

The xenobiotic oxidation polymorphism associated with cytochrome P450 2D6 (CYP2D6) was investigated in 152 genetically related and unrelated healthy Inuit subjects living in the High Arctic of eastern Canada. Phenotyping was based on HPLC determination of the CYP2D6-related dextromethorphan metabolic ratio in overnight urine samples after oral administration of 30 mg dextromethorphan hydrobromide. The log metabolic ratio was bimodally distributed, with three subjects classified as poor metabolizers (PMs). In subjects unrelated in the first degree, the incidence of the PM phenotype was 3 of 90 or 3.3%. PCR-based analyses of DNA for variants of the CYP2D6 gene demonstrated that the PMs of dextromethorphan had the defective allele CYP2D6*4. The estimated frequency of the CYP2D6*4 allele was 0.067-0.083, which is lower than the frequency in Caucasians but higher than the frequency in Oriental populations. The CYP2D6*3 and the CYP2D6*6 alleles were not detected in the Inuit population. The CYP2D6*10 allele was present in only four unrelated subjects, classified as extensive metabolizers (EMs), resulting in an estimated allele frequency of 0.022, which is much lower than in Oriental populations. This study demonstrated the existence of the CYP2D6 polymorphism in Canadian Inuit, while the frequencies of allelic variants of CYP2D6 point to the uniqueness of this population. Several important therapeutic drugs that are being prescribed in Arctic communities will have altered pharmacokinetics in PMs of CYP2D6.

Detailed gene mapping data are provided for members of a Yugoslavian and Canadian family with a thalassemia heterozygosity characterized by mild anemia with severe microcytosis and hypochromia, normal levels of Hb A2 and slightly raised Hb F levels. The condition in both families results from large deletions (minimally approximately 148 kb in the Yugoslavian family and minimally approximately 185 kb in the Canadian family), which include all functional and psi genes of the beta globin gene cluster. The Canadian propositus was a newborn baby who has been followed for nearly 2 years; severe anemia developed some 30-40 days after birth when the Hb F level was still 70%; recovery was evident at the age of 90 days when the Hb F level had decreased to 40%.