Annual pulses of copper-enriched sediment in a North American river downstream of a large lake following the catastrophic failure of a mine tailings storage facility.

Failures of mine tailings storage facilities (TSF) can have profound and long-lasting effects on the downstream receiving environment. Virtually all spills to date have been into river systems without large lakes that may buffer downstream impacts. In August 2014, the failure of the Mount Polley copper (Cu)-gold mine TSF in British Columbia, Canada, released ~25 × 106 m3 of water and solids; globally, this is the second largest TSF spill in history. Over 18 × 106 m3 was delivered to Quesnel Lake, which is ~9 km from the TSF and is the third deepest lake in North America, and a crucial habitat for Pacific salmon and trout populations. We determined the sediment-associated Cu concentrations and fluxes in Quesnel River, downstream of the lake, from August 2014 to February 2021 based on the analysis of >400 samples of sediment, mainly collected using a continuous-flow centrifuge. During each winter since the spill, Cu concentrations in the fluvial sediment in the upper reaches of the river (~35 km from the TSF) were elevated relative to regional background concentrations and samples collected before the spill. Maximum Cu concentrations were ~410 mg kg-1 which exceeds Canadian sediment quality guidelines for the protection of aquatic organisms (197 mg kg-1). Monitoring of Quesnel Lake since the spill shows that these annual pulses in the winter are due to resuspension of unconsolidated tailings and sediments at the bottom of Quesnel Lake, during autumnal lake turnover, which become mixed throughout the water column and subsequently flow into Quesnel River. Results show that while large lakes may buffer downstream aquatic systems from contaminated sediment, they may prolong the environmental impact. These findings are crucial in understanding how lake processes may modify the effects of TSF spills on downstream aquatic systems.

The bacterial community of Quesnel Lake sediments impacted by a catastrophic mine tailings spill differ in composition from those at undisturbed locations - two years post-spill.

The West Basin of Quesnel Lake (British Columbia, Canada) suffered a catastrophic disturbance event in August 2014 when mine tailings and scoured natural material were deposited into the lake's West Basin due to an impoundment failure at the adjacent Mount Polley copper-gold mine. The deposit covered a significant portion of the West Basin floor with a thick layer of material. Since lake sediments host bacterial communities that play key roles in the geochemical cycling in lacustrine environments, it is important to understand which groups inhabit the newly deposited material and what this implies for the ecological function of the West Basin. Here we report a study conducted two years post-spill, comparing the bacterial communities from sediments of both disturbed and undisturbed sites. Our results show that sediments from disturbed sites differed in physical and chemical properties than those in undisturbed sites (e.g. higher pH, particle size and Cu concentration). Furthermore, bacterial communities from the disturbed sites appeared to be legacy communities from the tailings impoundment, with metabolic potential revolving mainly around the cycling of S and metals, whereas the ones from the undisturbed sites were associated with the cycling of N.

SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia.

Constitutional dominant loss-of-function mutations in the SPRED1 gene cause a rare phenotype referred as neurofibromatosis type 1 (NF1)-like syndrome or Legius syndrome, consisted of multiple café-au-lait macules, axillary freckling, learning disabilities and macrocephaly. SPRED1 is a negative regulator of the RAS MAPK pathway and can interact with neurofibromin, the NF1 gene product. Individuals with NF1 have a higher risk of haematological malignancies. SPRED1 is highly expressed in haematopoietic cells and negatively regulates haematopoiesis. SPRED1 seemed to be a good candidate for leukaemia predisposition or transformation. We performed SPRED1 mutation screening and expression status in 230 paediatric lymphoblastic and acute myeloblastic leukaemias (AMLs). We found a loss-of-function frameshift SPRED1 mutation in a patient with Legius syndrome. In this patient, the leukaemia blasts karyotype showed a SPRED1 loss of heterozygosity, confirming SPRED1 as a tumour suppressor. Our observation confirmed that acute leukaemias are rare complications of the Legius syndrome. Moreover, SPRED1 was significantly decreased at RNA and protein levels in the majority of AMLs at diagnosis compared with normal or paired complete remission bone marrows. SPRED1 decreased expression correlated with genetic features of AML. Our study reveals a new mechanism which contributes to deregulate RAS MAPK pathway in the vast majority of paediatric AMLs.

Reconstruction of limnology and microbialite formation conditions from carbonate clumped isotope thermometry.

Quantitative tools for deciphering the environment of microbialite formation are relatively limited. For example, the oxygen isotope carbonate-water geothermometer requires assumptions about the isotopic composition of the water of formation. We explored the utility of using 'clumped' isotope thermometry as a tool to study the temperatures of microbialite formation. We studied microbialites recovered from water depths of 10-55 m in Pavilion Lake, and 10-25 m in Kelly Lake, spanning the thermocline in both lakes. We determined the temperature of carbonate growth and the (18)O/(16)O ratio of the waters that microbialites grew in. Results were then compared to current limnological data from the lakes to reconstruct the history of microbialite formation. Modern microbialites collected at shallow depths (11.7 m) in both lakes yield clumped isotope-based temperatures of formation that are within error of summer water temperatures, suggesting that clumped isotope analyses may be used to reconstruct past climates and to probe the environments in which microbialites formed. The deepest microbialites (21.7-55 m) were recovered from below the present-day thermoclines in both lakes and yield radioisotope ages indicating they primarily formed earlier in the Holocene. During this time, pollen data and our reconstructed water (18)O/(16)O ratios indicate a period of aridity, with lower lake levels. At present, there is a close association between both photosynthetic and heterotrophic communities, and carbonate precipitation/microbialite formation, with biosignatures of photosynthetic influences on carbonate detected in microbialites from the photic zone and above the thermocline (i.e., depths of generally <20 m). Given the deeper microbialites are receiving <1% of photosynthetically active radiation (PAR), it is likely these microbialites primarily formed when lower lake levels resulted in microbialites being located higher in the photic zone, in warm surface waters.

Determinants of vaccination coverage for children and teenagers.

UNLABELLED: The official vaccinal program is updated every year. Nevertheless, the observed vaccination coverage does not correspond to the recommended program. OBJECTIVE: Our objective was to identify factors influencing vaccinal practice, especially for hepatitis B. METHOD: We sent a questionnaire to two medical populations of the French Loire subdivision: 100 randomly chosen general practitioners, and 53 pediatricians and physicians working for public office for mother and childcare. RESULTS: The updated official recommendations were considered as the reference document for both populations. The study did not reveal any hesitation or lack of information, which could explain the low hepatitis B vaccinal coverage. Eighty-five percent of questioned physicians claimed having changed their practice, thanks to the easy use of Infanrix Hexa®, probably explaining the current improvement of hepatitis B vaccinal coverage rate.

ATM-dependent expression of IEX-1 controls nuclear accumulation of Mcl-1 and the DNA damage response.

The early-response gene product IEX-1 (also known as IER3) was recently found to interact with the anti-apoptotic Bcl-2 family member, myeloid cell leukemia-1 (Mcl-1). In this study we show that this interaction specifically and timely controls the accumulation of Mcl-1 in the nucleus in response to DNA damage. The IEX-1 protein is rapidly induced by γ-irradiation, genotoxic agents or replication inhibitors, in a way dependent on ataxia telangiectasia mutated (ATM) activity and is necessary for Mcl-1 nuclear translocation. Conversely, IEX-1 protein proteasomal degradation triggers the return of Mcl-1 to the cytosol. IEX-1 and Mcl-1 are integral components of the DNA damage response. Loss of IEX-1 or Mcl-1 leads to genomic instability and increased sensitivity to genotoxic and replicative stresses. The two proteins cooperate to maintain Chk1 activation and G2 checkpoint arrest. Mcl-1 nuclear translocation may foster checkpoint and improve the tumor resistance to DNA damage-based cancer therapies. Deciphering the pathways involved in IEX-1 degradation should lead to the discovery of new therapeutic targets to increase sensitivity of tumor cells to chemotherapy.

Constraining carbon sources and growth rates of freshwater microbialites in Pavilion Lake using (14)C analysis.

This study determined the natural abundance isotopic compositions ((13)C, (14)C) of the primary carbon pools and microbial communities associated with modern freshwater microbialites located in Pavilion Lake, British Columbia, Canada. The Delta(14)C of dissolved inorganic carbon (DIC) was constant throughout the water column and consistent with a primarily atmospheric source. Observed depletions in DIC (14)C values compared with atmospheric CO(2) indicated effects due either to DIC residence time and/or inputs of (14)C-depleted groundwater. Mass balance comparisons of local and regional groundwater indicate that groundwater DIC could contribute a maximum of 9-13% of the DIC. (14)C analysis of microbial phospholipid fatty acids from microbialite communities had Delta(14)C values comparable with lake water DIC, demonstrating that lake water DIC was their primary carbon source. Microbialite carbonate was also primarily derived from DIC. However, some depletion in microbialite carbonate (14)C relative to lake water DIC occurred, due either to residence time or mixing with a (14)C-depleted carbon source. A detrital branch covered with microbialite growth was used to estimate a microbialite growth rate of 0.05 mm year(-1) for the past 1000 years, faster than previous estimates for this system. These results demonstrate that the microbialites are actively growing and that the primary carbon source for both microbial communities and recent carbonate is DIC originating from the atmosphere. While these data cannot conclusively differentiate between abiotic and biotic formation mechanisms, the evidence for minor inputs of groundwater-derived DIC is consistent with the previously hypothesized biological origin of the Pavilion Lake microbialites.

Modern freshwater microbialite analogues for ancient dendritic reef structures.

Microbialites are organosedimentary structures that can be constructed by a variety of metabolically distinct taxa. Consequently, microbialite structures abound in the fossil record, although the exact nature of the biogeochemical processes that produced them is often unknown. One such class of ancient calcareous structures, Epiphyton and Girvanella, appear in great abundance during the Early Cambrian. Together with Archeocyathids, stromatolites and thrombolites, they formed major Cambrian reef belts. To a large extent, Middle to Late Cambrian reefs are similar to Precambrian reefs, with the exception that the latter, including terminal Proterozoic reefs, do not contain Epiphyton or Girvanella. Here we report the discovery in Pavilion Lake, British Columbia, Canada, of a distinctive assemblage of freshwater calcite microbialites, some of which display microstructures similar to the fabrics displayed by Epiphyton and Girvanella. The morphologies of the modern microbialites vary with depth, and dendritic microstructures of the deep water (> 30 m) mounds indicate that they may be modern analogues for the ancient calcareous structures. These microbialites thus provide an opportunity to study the biogeochemical interactions that produce fabrics similar to those of some enigmatic Early Cambrian reef structures.