Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study.

Background: Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. Objectives: We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. Design: This is a retrospective, multicentre study of patients admitted with ASUC. Methods: CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. Results: CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). Conclusion: CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.

Cytomegalovirus reactivation in acute severe ulcerative colitis Cytomegalovirus (CMV) is a highly prevalent virus that may result in concominant reactivation in patients with acute severe ulcerative colitis and potentially worsen their outcomes. Our study aims to determine the impact of presence of CMV in patients with acute severe ulcerate colitis requiring hospitalisation and its association with outcomes including risk of surgical resection of colon, length of hospital stay, readmission rate, as well as effect of outcomes amongst those treated with antivirals for CMV. Our results did not find a significant association between detection of CMV on surgical risk, though outcomes including longer hospital stays, higher readmission rate were found. Antiviral use was not associated with lower risk of surgery but was found to prolong time to surgery. Given that our study was based on retrospective data, further prospective studies will be required to examine the benefit of antiviral use in outcomes for those with concominant CMV and acute severe ulcerative colitis. We conclude from our study that while having concomitant CMV with acute severe uclerative colitis may not necessarily increase risk for surgery, patients may still have worse outcomes in other areas therefore the detection of CMV should be considered a significant and clinically relevant result.

Informing the Exposure Landscape: The Fate of Microplastics in a Large Pelagic In-Lake Mesocosm Experiment.

Understanding microplastic exposure and effects is critical to understanding risk. Here, we used large, in-lake closed-bottom mesocosms to investigate exposure and effects on pelagic freshwater ecosystems. This article provides details about the experimental design and results on the transport of microplastics and exposure to pelagic organisms. Our experiment included three polymers of microplastics (PE, PS, and PET) ranging in density and size. Nominal concentrations ranged from 0 to 29,240 microplastics per liter on a log scale. Mesocosms enclosed natural microbial, phytoplankton, and zooplankton communities and yellow perch (Perca flavescens). We quantified and characterized microplastics in the water column and in components of the food web (biofilm on the walls, zooplankton, and fish). The microplastics in the water stratified vertically according to size and density. After 10 weeks, about 1% of the microplastics added were in the water column, 0.4% attached to biofilm on the walls, 0.01% within zooplankton, and 0.0001% in fish. Visual observations suggest the remaining >98% were in a surface slick and on the bottom. Our study suggests organisms that feed at the surface and in the benthos are likely most at risk, and demonstrates the value of measuring exposure and transport to inform experimental designs and achieve target concentrations in different matrices within toxicity tests.

Eosinophilic Gastroenteritis Causing Pyloric Stenosis: A Rare Manifestation.

Eosinophilic gastritis is a gastrointestinal disorder characterized by eosinophilic infiltration in the gastric wall. We present a rare case of critical pyloric stenosis secondary to eosinophilic gastritis in a 16-year-old adolescent girl who presented with nausea, vomiting, early satiety, and abdominal pain. Abdominal computed tomography and subsequent esophagogastroduodenoscopy confirmed the anatomical diagnosis, but histological confirmation of the eosinophilic etiology was challenging. After an unsuccessful trial of high-dose systemic corticosteroids, a laparoscopic gastrojejunostomy was performed and long-term immunosuppression with mycophenolate mofetil was commenced.

A Multicompartment Assessment of Microplastic Contamination in Semi-remote Boreal Lakes.

Microplastic contamination is ubiquitous across the globe, even in remote locations. Still, the sources and pathways of microplastics to such locations are largely unknown. To investigate microplastic contamination in a semi-remote location, we measured microplastic concentrations in nine oligotrophic lakes within and around the International Institute for Sustainable Development-Experimental Lakes Area in northwestern Ontario, Canada. Our first objective was to establish ambient concentrations of microplastics in bottom sediments, surface water, and atmospheric deposition in semi-remote boreal lakes. Across all lakes, mean shallow and deep sediment microplastic concentrations, near-surface water microplastic concentrations from in situ filtering, and dry atmospheric microplastic deposition rates were 551 ± 354 particles kg-1, 177 ± 103 particles kg-1, 0.2 ± 0.3 particles L-1, and 0.4 ± 0.2 particles m-2 day-1, respectively. Our second objective was to investigate whether microplastic contamination of these lakes is driven by point sources including local runoff and direct anthropogenic inputs or nonpoint sources such as atmospheric deposition. Lakes were selected based on three levels of anthropogenic activity-low, medium, and high-though activity levels were minimal across all study lakes compared with highly populated areas. Whereas a positive correlation would indicate that point sources were a likely pathway, we observed no relationship between the level of anthropogenic activity and microplastic contamination of surface water. Moreover, the composition of microplastics in surface water and atmospheric deposition were similar, comprising mostly polyester and acrylic fibers. Together, these results suggest that atmospheric deposition may be the main pathway of microplastics to these remote boreal lakes. Environ Toxicol Chem 2024;43:999-1011. © 2024 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Freshwater connectivity transforms spatially integrated signals of biodiversity.

Aquatic ecosystems offer a continuum of water flow from headwater streams to inland lakes and coastal marine systems. This spatial connectivity influences the structure, function and dynamics of aquatic communities, which are among the most threatened and degraded on the Earth. Here, we determine the spatial resolution of environmental DNA (eDNA) in dendritic freshwater networks, which we use as a model for connected metacommunities. Our intensive sampling campaign comprised over 420 eDNA samples across 21 connected lakes, allowing us to analyse detections at a variety of scales, from different habitats within a lake to entire lake networks. We found strong signals of within-lake variation in eDNA distribution reflective of typical habitat use by both fish and zooplankton. Most importantly, we also found that connecting channels between lakes resulted in an accumulation of downstream eDNA detections in lakes with a higher number of inflows, and as networks increased in length. Environmental DNA achieves biodiversity surveys in these habitats in a high-throughput, spatially integrated way. These findings have profound implications for the interpretation of eDNA detections in aquatic ecosystems in global-scale biodiversity monitoring observations.

Isotopic-based evidence for reduced benthic contributions to fish after a whole-lake addition of nanosilver.

Silver nanoparticles (AgNPs) are added as antibacterial and anti-odor agents to a wide range of textiles, with high potential for release into aquatic environments via domestic wastewater. Previous work demonstrating the negative impacts of AgNP exposure on periphyton production suggests benthic primary production could be reduced in aquatic ecosystems impacted by AgNP discharge. To evaluate the potential for AgNPs to alter benthic-pelagic coupling in aquatic ecosystems, tissue-stable isotope ratios of carbon and nitrogen from northern pike (Esox lucius) and yellow perch (Perca flavescens) were measured before, during, and after the addition of AgNPs to a whole-lake ecosystem, and compared to those collected from a nearby reference lake. A shift in carbon isotope ratios toward more negative values was observed in both P. flavescens and E. lucius collected from the lake where AgNPs were added, with no shift in similar magnitude observed in E. lucius from the reference lake. Consequently, Bayesian estimates of benthic energy consumed decreased by 32% for P. flavescens and by 40% for E. lucius collected after AgNP additions relative to pre-addition estimates, greater in magnitude or opposite in direction of trends observed in our reference lake. Analyses suggest no changes in fish nitrogen isotope ratios related to AgNP additions. We hypothesize that the observed reduction in littoral energy use of fish reported here is a response to AgNP settling in littoral benthic habitats-the main habitat in lakes supporting periphyton-as AgNP has been shown elsewhere to significantly reduce the rates of periphyton production. Further, our study highlights the need to broaden the scope of risk assessments for AgNPs and other emerging contaminants prone to settling to consider habitat-specific impacts on resource utilization by organisms after their release into aquatic ecosystems.

Determining efficacy of dynamic multimedia bowel preparation instructions versus standard instructions on adenoma detection and patient reported measures (DIGICLEAN trial): a study protocol for a multicentre, colonoscopist-blinded, randomised controlled trial.

INTRODUCTION: Colonoscopy plays important roles in bowel cancer screening and treatment. Poor bowel preparation occurs in 20-25% of colonoscopies. This negatively impacts adenoma and sessile serrated lesion detection rates, procedural time, requirement for repeat colonoscopies, healthcare costs and likelihood of patient withdrawal from screening programmes. It is unclear whether a combination of multimedia modalities can improve bowel preparation quality, adenoma detection rates and patient-reported measures in those undergoing colonoscopy assessment. METHODS: The DIGICLEAN trial is a prospective, parallel, multicentre, colonoscopist-blinded, randomised controlled trial. The trial will enrol 1294 participants aged 45 years and older who are indicated for a colonoscopy as an outpatient with a positive faecal occult blood test, iron deficiency anaemia or rectal bleeding. Participants will be randomised into the interventional arm, where bowel preparation instructions are delivered via a web-based application which uses scheduled short messaging service, regular patient survey assessment, email and videos; or the control arm, where routine standard written, verbal or emailed instructions are administered. The web-based application will assess patient-reported bloating, constipation and dietary adherence leading up to the colonoscopy. Depending on patient responses, additional aperients may be encouraged digitally in the interventional arm with same instructions made available in written format for the control arm. Patient-reported measures will be collected in both arms the day after the procedure using the validated Newcastle ENDOPREM questionnaire. In some sites, participants will undergo digital pre-anaesthetic screening as well. The co-primary endpoints are the adenoma detection rates and patient-reported measures taken after the colonoscopy. ETHICS AND DISSEMINATION: Ethics approval for this study was obtained from the Western Sydney Local Health District Human Research Ethics Committee (2022/ETH00059). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000747729.

Aeolus winds impact on volcanic ash early warning systems for aviation.

Forecasting volcanic ash atmospheric pathways is of utmost importance for aviation. Volcanic ash can interfere with aircraft navigational instruments and can damage engine parts. Early warning systems, activated after volcanic eruptions can alleviate the impacts on aviation by providing forecasts of the volcanic ash plume dispersion. The quality of these short-term forecasts is subject to the accuracy of the meteorological wind fields used for the initialization of regional models. Here, we use wind profiling data from the first high spectral resolution lidar in space, Aeolus, to examine the impact of measured wind fields on regional NWP and subsequent volcanic ash dispersion forecasts, focusing on the case of Etna's eruption on March 2021. The results from this case study demonstrate a significant improvement of the volcanic ash simulation when using Aeolus-assimilated meteorological fields, with differences in wind speed reaching up to 8 m/s when compared to the control run. When comparing the volcanic ash forecast profiles with downwind surface-based aerosol lidar observations, the modeled field is consistent with the measurements only when Aeolus winds are assimilated. This result clearly demonstrates the potential of Aeolus and highlights the necessity of future wind profiling satellite missions for improving volcanic ash forecasting and hence aviation safety.

Phases of Match-Play in Professional Australian Football: Positional Demands and Match-Related Fatigue.

This study examined the influence of player position and match quarter on activity profiles during the phases of play in Australian Football. Global positioning satellite data was collected for one season from an Australian Football League team for nomadic, key position and ruck players (age: 24.8 ± 4.2 years, body mass: 88.3 ± 8.7 kg, height: 1.88 ± 0.8 m). Separate linear mixed models and effect sizes were used to analyse differences between positions and game quarter within each phase of play for values of distance, speed and metabolic power indices. There were clear differences between positions for low-speed running, high-speed running, total distance and average speed. Nomadic players generally recorded the highest match running outputs, followed by key position players and ruckmen. Within each position, offence and defence involved the highest intensities, followed by contested play and then stoppage periods. Across the four quarters, there were small to large reductions in average speed, high-speed running, high power and energy expenditure during offence, defence and contested play, but not during stoppages. Accordingly, conditioning staff should consider the intermittent intensities of the phases of match-play for each position to optimally prepare players for competition. Reductions in match intensities were evident during active periods of play providing implications for real-time monitoring to optimise the timing of rotations.

Environmental nucleic acids: A field-based comparison for monitoring freshwater habitats using eDNA and eRNA.

Nucleic acids released by organisms and isolated from environmental substrates are increasingly being used for molecular biomonitoring. While environmental DNA (eDNA) has received much attention, the potential of environmental RNA as a biomonitoring tool remains under-explored. Several recent studies using paired DNA and RNA metabarcoding of bulk samples suggest that RNA might better reflect "metabolically active" parts of the community. However, such studies mainly capture organismal eDNA and eRNA. For larger eukaryotes, isolation of extra-organismal RNA will be important, but viability needs to be examined in a field-based setting. In this study we evaluate (a) whether extra-organismal eRNA release from macroeukaryotes can be detected given its supposedly rapid degradation, and (b) if the same field collection methods for eDNA can be applied to eRNA. We collected eDNA and eRNA from water in lakes where fish community composition is well documented, enabling a comparison between the two nucleic acids in two different seasons with monitoring using conventional methods. We found that eRNA is released from macroeukaryotes and can be filtered from water and metabarcoded in a similar manner as eDNA to reliably provide species composition information. eRNA had a small but significantly greater true positive rate than eDNA, indicating that it correctly detects more species known to exist in the lakes. Given relatively small differences between the two molecules in describing fish community composition, we conclude that if eRNA provides significant advantages in terms of lability, it is a strong candidate to add to the suite of molecular monitoring tools.

Mercury methylation and methylmercury demethylation in boreal lake sediment with legacy sulphate pollution.

Sulphate and dissolved organic matter (DOM) in freshwater systems may regulate the formation of methylmercury (MeHg), a potent neurotoxin that biomagnifies in aquatic ecosystems. While many boreal lakes continue to recover from decades of elevated atmospheric sulphate deposition, little research has examined whether historically high sulphate concentrations can result in persistently elevated MeHg production and accumulation in aquatic systems. This study used sediment from a historically sulphate-impacted lake and an adjacent reference lake in northwestern Ontario, Canada to investigate the legacy effects of sulphate pollution, as well as the effects of newly added sulphate, natural organic matter (NOM) of varying sulphur content and a sulphate reducing bacteria (SRB) inhibitor on enhancing or inhibiting the Hg methylation and demethylation activity (Kmeth and Kdemeth) in the sediment. We found that Kmeth and MeHg concentrations in sulphate-impacted lake sediment were significantly greater than in reference lake sediment. Further adding sulphate or NOM with different sulphur content to sediment of both lakes did not significantly change Kmeth. The addition of a SRB inhibitor resulted in lower Kmeth only in sulphate-impacted sediment, but methylation was not entirely depressed. Methylmercury demethylation potentials in sediment were consistent across lakes and experimental treatments, except for some impacts related to SRB inhibitor additions in the reference lake sediment. Overall, a broader community of microbes beyond SRB may be methylating Hg and demethylating MeHg in this system. This study reveals that legacies of sulphate pollution in boreal lakes may persist for decades in stimulating elevated Hg methylation in sediment.

Whole-lake nanosilver additions reduce northern pike (Esox lucius) growth.

Nanosilver (AgNP) is an anti-microbial agent widely used in consumer products, with significant potential for these nanoparticles to be released into aquatic environments. Laboratory studies involving short-term exposures of fish to AgNP show a range of toxicological effects, but these studies do not address potential responses in long-lived organisms resulting from chronic exposures. A collaborative study involving additions of AgNP to environmentally relevant concentrations over two field seasons took place at the IISD-Experimental Lakes Area, providing an opportunity to study the impacts of chronic exposures to long-lived fish species. In the present study, we evaluated the abundance and growth of an apex predator, Northern Pike (Esox lucius), collected from Lake 222 before, during and after the AgNP dosing period and compared results to those from a nearby unmanipulated lake (Lake 239). While the abundance of Northern Pike from Lake 222 during the study period was essentially stable, per capita availability of their primary prey species, Yellow Perch (Perca flavescens) declined by over 30%. Northern Pike fork length- and weight-at-age (indices of growth rate) declined following AgNP additions, most notably in age 4 and 5 fish. No similar changes in prey availability or growth were observed in Northern Pike from the reference lake. Body condition did not change in Northern Pike collected from either Lake 222 or Lake 239. Our results indicate that declines in the growth of Northern Pike chronically exposed to AgNP likely resulted from reduced prey availability but direct sublethal effects from AgNP exposure could also have been a factor. The persistence of reduced growth in Northern Pike two years after the cessation of AgNP additions highlight the potential legacy impacts of this contaminant once released into aquatic ecosystems.

Tactical analysis of individual and team behaviour in professional Australian Football.

INTRODUCTION: This study sought to reduce the dimensionality of commonly reported spatiotemporal characteristics obtained from Australian Football games to facilitate their practical use and interpretability. METHODS: A retrospective longitudinal design was utilised with team and individual spatiotemporal variables, measured via global navigation satellite system devices, collected during official Australian Football League matched over three seasons. Two separate principal component analyses were conducted at the team and individual level to reduce correlated spatiotemporal characteristics into a smaller set of uncorrelated components. RESULTS: At the team level, eighteen variables were reduced to five components pertaining to dispersive coordination, lateral predictability and spacing, multidirectional synchrony, longitudinal predictability and longitudinal behaviour whilst maintaining 69% of variance in the original dataset. At the individual level, fifteen variables were reduced to four components pertaining to multidirectional and spacing synchrony, unpredictability, player movement and player positioning whilst maintaining 64% of variance. CONCLUSION: This study is the first to provide a simplified, novel method for analysing spatiotemporal behaviour in an Australian Football context with both the team- and individual- derived metrics revealing useful information for coaches and practitioners. Components may provide insight into behaviours that emerge and persist throughout a game and allow coaches to distinguish between different playing/behavioural styles.

Alternative migratory strategies related to life history differences in the Walleye (Sander vitreus).

BACKGROUND: While Pace of Life Syndrome predicts behavioural differences between individuals with differential growth and survival, testing these predictions in nature is challenging due to difficulties with measuring individual behaviour in the field. However, recent advances in acoustic telemetry technology have facilitated measurements of individual behaviour at scales not previously possible in aquatic ecosystems. METHODS: Using a Walleye (Sander vitreus) population inhabiting Black Bay, Lake Superior, we examine whether life history characteristics differ between more and less mobile individuals as predicted by Pace of Life Syndrome. We tracked the movement of 192 individuals from 2016 to 2019 using an acoustic telemetry study, relating patterns in annual migratory behaviour to individual growth, and seasonal changes in optimal thermal-optical habitat. RESULTS: We observed two consistent movement patterns in our study population-migratory individuals left Black Bay during late summer to early fall before returning to the bay, whereas residents remained within the bay year-round. The average maximum length of migrant Walleye was 5.5 cm longer than residents, and the sex ratios of Walleye caught during fall surveys was increasingly female-biased towards the mouth of Black Bay, suggesting that a majority of migrants were females. Further, Walleye occupancy outside of Black Bay was positively associated with increasing thermal-optical habitat. CONCLUSIONS: Walleye in Black Bay appear to conform to Pace of Life Syndrome, with migrant individuals gaining increased fitness through increased maximum size, which, given size-dependent fecundity in this species, likely results in greater reproductive success (via greater egg deposition vs. non-migrants). Further, apparent environmental (thermal) controls on migration suggest that migratory Walleye (more so than residents) may be more sensitive to changing environmental conditions (e.g., warming climate) than residents.

A synthesis of senescence predictions for indeterminate growth, and support from multiple tests in wild lake trout.

Senescence-the deterioration of functionality with age-varies widely across taxa in pattern and rate. Insights into why and how this variation occurs are hindered by the predominance of laboratory-focused research on short-lived model species with determinate growth. We synthesize evolutionary theories of senescence, highlight key information gaps and clarify predictions for species with low mortality and variable degrees of indeterminate growth. Lake trout are an ideal species to evaluate predictions in the wild. We monitored individual males from two populations (1976-2017) longitudinally for changes in adult mortality (actuarial senescence) and body condition (proxy for energy balance). A cross-sectional approach (2017) compared young (ages 4-10 years) and old (18-37 years) adults for (i) phenotypic performance in body condition, and semen quality-which is related to fertility under sperm competition (reproductive senescence)-and (ii) relative telomere length (potential proxy for cellular senescence). Adult growth in these particular populations is constrained by a simplified foodweb, and our data support predictions of negligible senescence when maximum size is only slightly larger than maturation size. Negative senescence (aka reverse senescence) may occur in other lake trout populations where diet shifts allow maximum sizes to greatly exceed maturation size.

Match simulation practice may not represent competitive match play in professional Australian football.

Match simulation in team sport should sample representative constraints and behaviours to those observed in competitive matches to enhance near skill transfer. This study compared task constraints (field length, field width, length per width ratio, space per player), time-standardised skill metrics (goals, shots on goal, handballs, kicks, marks, turnovers, tackles, handball proficiency, kick proficiency) and cooperative passing metrics (connectedness, indegree variability and outdegree variability) between match simulation practice and competitive Australian Football League (AFL) games for one professional team. MANOVAs identified activity-related differences for task constraints, skill metrics and cooperative passing networks. During match simulation, goals were scored more frequently, but with less passing actions per minute. Receiving and distributing passing networks were more centralised (reliance on fewer key individuals), with less turnovers and tackles per minute compared to AFL matches. If match simulation is designed to reflect competition, then player and team skill preparation may be compromised. Furthermore, the competing demands in high-performance sport may restrict the degree of representativeness that can be achieved during practice. These findings provide valuable insight and may assist practitioners and/or coaches to understand the value of match simulation practice and to maximise near skill transfer from match simulation to competition.

Mammalian Deubiquitinating Enzyme Inhibitors Display in Vitro and in Vivo Activity against Malaria Parasites and Potentiate Artemisinin Action.

The ubiquitin proteasome system (UPS) is an emerging drug target in malaria due to its essential role in the parasite's life cycle stages as well its contribution to resistance to artemisinins. Polymorphisms in the Kelch13 gene of Plasmodium falciparum are primary markers of artemisinin resistance and among other things are phenotypically characterized by an overactive UPS. Inhibitors targeting the proteasome, critical components of the UPS, display activity in malaria parasites and synergize artemisinin action. Here we report the activity of small molecule inhibitors targeting mammalian deubiquitinating enzymes, DUBs (upstream UPS components), in malaria parasites. We show that generic DUB inhibitors can block intraerythrocytic development of malaria parasites in vitro and possess antiparasitic activity in vivo and can be used in combination with additive to synergistic effect. We also show that inhibition of these upstream components of the UPS can potentiate the activity of artemisinin in vitro as well as in vivo to the extent that artemisinin resistance can be overcome. Combinations of DUB inhibitors anticipated to target different DUB activities and downstream proteasome inhibitors are even more effective at improving the potency of artemisinins than either inhibitors alone, providing proof that targeting multiple UPS activities simultaneously could be an attractive approach to overcoming artemisinin resistance. These data further validate the parasite UPS as a target to both enhance artemisinin action and potentially overcome resistance. Lastly, we confirm that DUB inhibitors can be developed into in vivo antimalarial drugs with promise for activity against all of human malaria and could thus further exploit their current pursuit as anticancer agents in rapid drug repurposing programs.

Thermal stratification and fish thermal preference explain vertical eDNA distributions in lakes.

Significant advances have been made towards surveying animal and plant communities using DNA isolated from environmental samples. Despite rapid progress, we lack a comprehensive understanding of the "ecology" of environmental DNA (eDNA), particularly its temporal and spatial distribution and how this is shaped by abiotic and biotic processes. Here, we tested how seasonal variation in thermal stratification and animal habitat preferences influences the distribution of eDNA in lakes. We sampled eDNA depth profiles of five dimictic lakes during both summer stratification and autumn turnover, each containing warm- and cool-water fishes as well as the cold-water stenotherm, lake trout (Salvelinus namaycush). Habitat use by S. namaycush was validated by acoustic telemetry and was significantly related to eDNA distribution during stratification. Fish eDNA became "stratified" into layers during summer months, reflecting lake stratification and the thermal niches of the species. During summer months, S. namaycush, which rarely ventured into shallow waters, could only be detected at the deepest layers of the lakes, whereas the eDNA of warm-water fishes was much more abundant above the thermocline. By contrast, during autumn lake turnover, the fish species assemblage as detected by eDNA was homogenous throughout the water column. These findings contribute to our overall understanding of the "ecology" of eDNA within lake ecosystems, illustrating how the strong interaction between seasonal thermal structure in lakes and thermal niches of species on very localized spatial scales influences our ability to detect species.

Multi-Level Responses of Yellow Perch (Perca flavescens) to a Whole-Lake Nanosilver Addition Study.

Silver nanoparticles (AgNP) are widely used as antibacterial agents in both commercial products and for industrial applications. As such, AgNP has a high potential for release into freshwater environments. As part of a whole-lake ecosystem experiment to examine the impacts of AgNP exposure at low µg/L concentrations over multiple years, we evaluated biological responses in Yellow Perch (Perca flavescens) before, during, and after AgNP additions to a freshwater lake. Yellow Perch were monitored for responses to in situ AgNP additions at the cellular (suite of biomarkers), individual (growth, prey consumption, and metabolism), and population (abundance and gross prey consumption) scales. At the cellular level, several biomarkers of oxidative stress in liver tissues revealed down-regulation, including decreased mRNA levels of catalase and glutathione peroxidase in Yellow Perch collected during AgNP exposure, and elevated ratios of reduced to oxidized glutathione. At the individual level, Yellow Perch bioenergetic models revealed that prey consumption and total metabolism significantly declined during AgNP additions and remained depressed one year after AgNP addition. At the population level, Yellow Perch densities and gross prey consumption declined after AgNP was added to the lake. Together, these results reveal a holistic assessment of the negative impacts of chronic exposure to environmentally relevant AgNP concentrations (i.e., µg/L) on Yellow Perch at cellular, individual, and population levels.

Experimentally Engineered Mutations in a Ubiquitin Hydrolase, UBP-1, Modulate In Vivo Susceptibility to Artemisinin and Chloroquine in Plasmodium berghei.

As resistance to artemisinins (current frontline drugs in malaria treatment) emerges in Southeast Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other regions where malaria is endemic. Reduced susceptibility to artemisinin in Southeast Asia has been primarily linked to mutations in the Plasmodium falciparum Kelch-13 gene, which is currently widely recognized as a molecular marker of artemisinin resistance. However, two mutations in a ubiquitin hydrolase, UBP-1, have been previously associated with reduced artemisinin susceptibility in a rodent model of malaria, and some cases of UBP-1 mutation variants associated with artemisinin treatment failure have been reported in Africa and SEA. In this study, we employed CRISPR-Cas9 genome editing and preemptive drug pressures to test these artemisinin susceptibility-associated mutations in UBP-1 in Plasmodium berghei sensitive lines in vivo Using these approaches, we show that the V2721F UBP-1 mutation results in reduced artemisinin susceptibility, while the V2752F mutation results in resistance to chloroquine (CQ) and moderately impacts tolerance to artemisinins. Genetic reversal of the V2752F mutation restored chloroquine sensitivity in these mutant lines, whereas simultaneous introduction of both mutations could not be achieved and appears to be lethal. Interestingly, these mutations carry a detrimental growth defect, which would possibly explain their lack of expansion in natural infection settings. Our work provides independent experimental evidence on the role of UBP-1 in modulating parasite responses to artemisinin and chloroquine under in vivo conditions.