Aquatic food webs and heavy metal contamination in the upper Blackfoot River, Montana

Acid mine drainage (AMD), characterized by low pH and abundant heavy metals, is a widespread problem affecting water quality and fish habitat in Montana. Montana’s upper Blackfoot River exhibits impaired water quality from historic mining that has significantly degraded aquatic habitat and reduced fish and invertebrate abundance in impacted streams. The goal of this study is to investigate the direct and indirect effects of mine-related heavy metals contamination on aquatic ecosystems by examining changes in aquatic community composition, bioaccumulation, and toxicity risk of heavy metals along a contamination gradient in the upper Blackfoot River. Three primary research questions were addressed in this study: 1) How are macro-invertebrate communities influenced by heavy metals contamination? 2) What are the implications of changes in food web structure for exposure pathways? 3) What levels of environmental contamination produce the greatest risk to upper trophic levels? Invertebrate and fish communities impacted by heavy metals in the upper Blackfoot River were sampled in 2009 and 2010 for community composition analyses and metals concentrations. The results of this study indicate that an increase in heavy metals contamination in the upper Blackfoot River results in important changes in exposure pathways of metals entering aquatic food webs through invertebrate food sources, as well as exposure pathways of metals to fish. The greatest exposure risk to upper trophic levels from the pool of bioavailable metals in invertebrates occurred at moderately contaminated sites where moderate invertebrate abundance and moderate sediment metals levels coincided. In addition, the highest metals concentrations in fish tissue were at sites with high exposure values in invertebrates, rather than sites with the highest sediment contamination levels. The results of this study indicate that biological mechanisms influencing the movement of heavy metals in aquatic food webs are important factors for assessing toxicity risk to upper trophic levels that may not be evident when considering environmental contamination alone

METAL CONTAMINATION AND FOOD WEB CHANGES ALTER EXPOSURE TO UPPER TROPHIC LEVELS IN UPPER BLACKFOOT RIVER BASIN STREAMS, MONTANA

Reduced invertebrate abundance and diversity are common responses to metals contamination in mining-impacted streams. The resulting changes in community composition may have implications for metals accumulation and transfer through the food web. We investigated how changes in invertebrate community composition (abundance, species richness, and food web complexity) influence metals bioaccumulation and exposure risk to upper trophic levels along a contamination gradient in the upper Blackfoot River Basin, Montana. Invertebrate species richness exhibited the strongest decline with increasing sediment metals concentrations, driven by the loss of metals-sensitive taxa. These changes in invertebrate community composition resulted in a decline in the proportion of invertebrates in the scraper functional feeding group, likely influencing dietary metals exposure to the invertebrate community. Additionally, invertebrates with a strong propensity-to-drift increased with sediment contamination, potentially facilitating metals transfer to fish and higher trophic levels through predation. Using invertebrate exposure values (invertebrate abundance x metals concentrations), we found that moderately contaminated sites in our study area produced both the highest invertebrate exposure values and the highest fish tissue metals concentrations. Considering both changes in invertebrate community composition and metal concentrations is an important step towards understanding and evaluating potential toxic effects to upper trophic levels in mining-impacted streams. Note that there are several datasets associated with this article

Dataset for the article: Metal contamination and food web changes alter exposure to upper trophic levels in upper Blackfoot River basin streams, Montana

Reduced invertebrate abundance and diversity are common responses to heavy metals contamination in mining-impacted streams. The resulting changes in community composition may have implications for metals accumulation and transfer through the food web. We investigated how changes in invertebrate community composition (abundance, species richness, and food web complexity) influence metals bioaccumulation and exposure risk to upper trophic levels along a contamination gradient in the upper Blackfoot River basin, Montana. Invertebrate species richness exhibited the strongest decline with increasing sediment metals concentrations, driven by the loss of metals-sensitive taxa. These changes in invertebrate community composition resulted in a decline in the proportion of invertebrates in the scraper functional feeding group, likely influencing dietary metals exposure to the invertebrate community. Additionally, invertebrates with a strong propensity-to-drift increased with sediment contamination, potentially facilitating metals transfer to fish and higher trophic levels through predation. By using invertebrate exposure values (invertebrate abundance x metals concentrations), we found that moderately contaminated sites in our study area produced both the highest invertebrate exposure values and the highest metals concentrations in fish tissues. Our results indicate that considering both changes in invertebrate community composition and metal concentrations is an important step towards understanding and evaluating potential toxic effects to upper trophic levels in mining-impacted streams. Geographic location: Upper Blackfoot River, Montana and tributaries in the vicinity of the Upper Blackfoot Mining Complex Associated data and attachments (files available below): Water quality [Water_quality.csv] Fine sediment metals [Fine_sediment_metals.csv] Invertebrate community composition [Invertebrate_community_composition.csv] Invertebrate metals concentrations [Invertebrate_metals.csv] Fish tissue metals [Fish_metals.csv] Fish population estimate [Fish_population.csv] Site descriptions [Site_descriptions.csv] Site map [Site_map.pdf] (see Download button above

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis

NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

ALS-associated missense and nonsense TBK1 mutations can both cause loss of kinase function

Mutations in TBK1 have been linked to amyotrophic lateral sclerosis (ALS). Some TBK1 variants are nonsense and are predicted to cause disease through haploinsufficiency, however many other mutations are missense with unknown functional effect. We exome sequenced 699 familial ALS patients and identified 16 TBK1 novel or extremely rare protein changing variants. We characterised a subset of these: p.G217R, p.R357X and p.C471Y. Here we show that the p.R357X and p.G217R both abolish the ability of TBK1 to phosphorylate two of its kinase targets, IRF3 and OPTN and to undergo phosphorylation. They both inhibit binding to OPTN and the p.G217R, within the TBK1 kinase domain, reduces homodimerisation, essential for TBK1 activation and function. Lastly, we show that the proportion TBK1 that is active (phosphorylated) is reduced in five lymphoblastoid cell lines derived from patients harbouring heterozygous missense or in-frame deletion TBK1 mutations. We conclude that missense mutations in functional domains of TBK1 impair the binding and phosphorylation of its normal targets, implicating a common loss of function mechanism, analogous to truncation mutations

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Vitamin and thyroid status in arctic grayling (Thymallus arcticus) exposed to doses of 3,3′,4,4′-tetrachlorobiphenyl that induce the phase I enzyme system

Induction of phase I biotransformation enzymes is recognized as a hallmark response in fish exposed to coplanar PCBs, Depletions of Vitamins A and E and disrupted thyroid hormone and glandular structure secondary to this induction have not yet been examined in an arctic fish species, Arctic grayling were exposed to a single oral dose of 0 (control), 10, 100 or 1000 ng 3,3′,4,4′-tetrachlorobiphenyl (TCB) g bodyweight, a contaminant found in most arctic fish, After 30 and 90 days of exposure, TCB concentrations in tissueS, hepatic phase I activity (as ethoxyresorufin-O-deethylase (EROD)), plasma and tissue vitamin A and E concentrations, plasma thyroid hormone levels and thyroid glandular structure were examined. Total plasma osmolality, as an indicator of overall fish health was also monitored. TCB recovery in tissues was low and extremely variable, making comparisons between intended dose groups inappropriate. Therefore, correlation analysis between actual recovered TCB concentrations and biochemical responses was employed. Hepatic EROD activity correlated strongly with liver TCB Concentrations. Liver concentrations of vitamin A were altered as a function of TCB concentrations and EROD activity, but plasma vitamin A status was not affected. Vitamin E was depleted by TCB accumulation in blood and EROD induction in liver of males only at 90 days post-exposure. Thyroid hormones status and glandular structure were not affected by the short duration TCB exposures used in this experiment. TCB concentrations were correlated with an elevation in plasma osmolality. Results from this experiment indicate that the vitamin status and osmoregulation of arctic grayling exposed to TCB can be compromised. Further studies of field populations exposed to this type of contaminant are warranted. Crown Copyright © 2001 Published by Elsevier Science Ltd. All rights reserved. -