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The increase in dissolved organic carbon (DOC) concentrations in freshwater systems has received considerable attention due to its implications for drinking water treatment and numerous limnological processes. While past studies have documented the influence of recovery from acidification and climate change on long-term DOC trends, the emerging importance of these explanatory factors remains less understood. In addition, few studies have followed up on recent trends in sites that have undergone increases in DOC. Using a dataset from 1980 to 2020, we investigated interannual variations in DOC and dissolved organic nitrogen (DON) in 49 lakes across four eastern Canadian regions with a history of increases in DOC. We identified recent shifts in DOC patterns using LOESS smoothing and piecewise regression. We observed a stabilizing pattern or even a decrease (p < 0.001) in high acidification regions (Dorset and Nova Scotia), where increases in DOC were previously documented. At the low acid deposition region, IISD-Experimental Lakes Area, an increasing pattern in DOC stabilized in the early 2000s; however, DOC appears to be increasing again in recent years (p = 0.03). Our analysis identified precipitation and SO 4 deposition as the primary explanatory variables for DOC patterns (explaining 56-71% of variance). However, because acid deposition has declined substantially, climate and local watershed factors are becoming increasingly influential, leading to the emergence of new DOC patterns. Long-term changes in DOC and DON were not always synchronous, as these were often correlated with different factors (e.g., DON with ammonium deposition). This resulted in observable shifts in DOC:DON ratios, indicative of changes in dissolved organic matter (DOM) composition. We underscore the importance of ongoing monitoring in diverse regions because of the changing nature of environmental variables and new emerging trends., 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 © 2024. Published by Elsevier Ltd.)

Understanding how species adapt to environmental change is necessary to protect biodiversity and ecosystem services. Growing evidence suggests species can adapt rapidly to novel selection pressures like predation from invasive species, but the repeatability and predictability of selection remain poorly understood in wild populations. We tested how a keystone aquatic herbivore, Daphnia pulicaria , evolved in response to predation pressure by the introduced zooplanktivore Bythotrephes longimanus . Using high-resolution 210 Pb-dated sediment cores from 12 lakes in Ontario (Canada), which primarily differed in invasion status by Bythotrephes , we compared Daphnia population genetic structure over time using whole-genome sequencing of individual resting embryos. We found strong genetic differentiation between populations approximately 70 years before versus 30 years after reported Bythotrephes invasion, with no difference over this period in uninvaded lakes. Compared with uninvaded lakes, we identified, on average, 64 times more loci were putatively under selection in the invaded lakes. Differentiated loci were mainly associated with known reproductive and stress responses, and mean body size consistently increased by 14.1% over time in invaded lakes. These results suggest Daphnia populations were repeatedly acquiring heritable genetic adaptations to escape gape-limited predation. More generally, our results suggest some aspects of environmental change predictably shape genome evolution.

Leaf dry matter content (LDMC) is an important determinant of plant flammability. Investigating global patterns of LDMC could provide insights into worldwide plant flammability patterns, informing wildfire management. We characterised global patterns of LDMC across 4074 species from 216 families, revealing that phylogenetic and environmental constraints influence LDMC. LDMC varied across growth forms and taxonomic groups, displaying phylogenetic niche conservatism. Temperature, precipitation, aridity index, soil total nitrogen content and wildfire activity affected LDMC, and the effect of wildfire activity was stronger than other environmental factors across species with postfire regeneration abilities. Such species had higher LDMC, and their LDMC was less phylogenetically conserved and more strongly associated with fire activity. Our results suggest that, although LDMC shows phylogenetic niche conservatism, LDMC is determined by environmental factors, especially wildfire activity. Wildfire has likely acted as a selective pressure towards high LDMC across species that persist through fire using postfire regeneration., (© 2025 John Wiley & Sons Ltd.)

In this study, the fluxes of microplastics (mp) were quantified during a 12-month period for three rural headwater lake catchments in Muskoka-Haliburton, south-central Ontario, Canada. A novel catchment particle balance approach was used, incorporating inputs from atmospheric deposition and stream inflows against lake outflow and sedimentation. This approach provides the first reported observation-based estimates of microplastic residence time in freshwater lakes. Atmospheric deposition had the highest daily microplastic flux (3.95-8.09 mp/m 2 /day), compared to the inflow streams (2.21-2.34 mp/m 2 /day), suggesting that it is the dominant source of microplastics to rural regions. Approximately 44-71% of the deposited microplastics were retained in the terrestrial catchments and 30-49% of the microplastics in the stream inflows were retained in the study lakes. Given that output fluxes ranged from 0.72-3.76 mp/m 2 /day in the sediment and 1.18-1.66 mp/m 2 /day in the lake outflows, the microplastic residence time was estimated to be between 3 and 12 years, suggesting that lakes are an important reservoir for microplastics. Fibers were the dominant shape in atmospheric deposition, streamwater, and lake water; however, in lake sediment, there was a higher proportion of fragments. Across all media, poly(ethylene terephthalate) was the dominant polymer identified (23%).

Plant flammability is an important driver of wildfires, and flammability itself is determined by several plant functional traits. While many plant traits are influenced by climatic conditions, the interaction between climatic conditions and plant flammability has rarely been investigated. Here, we explored the relationships among climatic conditions, shoot-level flammability components, and flammability-related functional traits for 186 plant species from fire-prone and nonfire-prone habitats. For species originating from nonfire-prone habitats, those from warmer areas tended to have lower shoot moisture content and larger leaves, and had higher shoot flammability with higher ignitibility, combustibility, and sustainability. Plants in wetter areas tended to have lower shoot flammability with lower combustibility and sustainability due to higher shoot moisture contents. In fire-prone habitats, shoot flammability was not significantly related to any climatic factor. Our study suggests that for species originating in nonfire-prone habitats, climatic conditions have influenced plant flammability by shifting flammability-related functional traits, including leaf size and shoot moisture content. Climate does not predict shoot flammability in species from fire-prone habitats; here, fire regimes may have an important role in shaping plant flammability. Understanding these nuances in the determinants of plant flammability is important in an increasingly fire-prone world., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

We studied the activity budgets of seven Ailurus fulgens , at three zoos within Australasia, using video cameras, and in-person observations. Red panda in this study followed a crepuscular activity pattern, with another short peak of activity around midnight. Ambient temperature greatly affected panda activity patterns; red panda allocated more time to resting and sleeping when temperatures increased. This preliminary study suggests how environmental factors affect captive red panda, which will help better inform captive facilities, and how this might impact their wild conspecifics.

Microplastics are ubiquitous in the environment; however, few studies have examined their abundance in atmospheric deposition in pristine environments, remote from anthropogenic emission sources. In the current study, atmospheric deposition samples were collected for 13 months (February 2019-March 2020) from four precipitation chemistry monitoring stations located in Muskoka-Haliburton, south-central Ontario, Canada. Anthropogenic particles (i.e., synthetic particles but not necessarily plastic) were observed at each station with an average deposition rate of 57 particles/m 2 /day (range from 32 to 73 particles/m 2 /day). Of the anthropogenic particles identified, 12% were plastic resulting in an average microplastic (mp) deposition rate of 7 mp/m 2 /day (range 4-9 mp/m 2 /day). Approximately 85% of the particles were fibres with fragments comprising only 15%. The most common particle colours were blue and red with 50% of the fragments and 84% of fibres being one of these two colours. Raman spectroscopy determined that polyamide and polyethylene terephthalate were the two most abundant polymers at 24% and 19%, respectively. Across the four stations anthropogenic particle concentrations were significantly related to wind speed (r s = 0.32 to 0.62) and temperature (r s = -0.53 to -0.84), with a noticeable increase in particle concentration when wind shifted from the west (average of 7.2 mp/L) to the south-east (average of 11.5 mp/L). Faster wind speed resulted in a larger airshed source area, and the seasonal effect associated with changes in temperature and wind direction led to changes in potential source regions that were contributing microplastics, such as the Greater Toronto Area (>200 km away)., Competing Interests: Declaration of competing interest The authors declare no competing financial or personal interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Mining and smelting activities have strongly influenced the Sudbury region (Ontario, Canada) since the late 19 th century, leading to acidification and metal contamination in many local ecosystems. Regulations on restricting acidic emissions were enacted in the 1970s, after which a considerable volume of paleolimnological work was completed to study the impacts of acidification on Sudbury-region lakes and their subsequent biological recovery. Twenty years after the last regional diatom-based assessment, many lakes have undergone large changes in limnological variables, including increases in pH and dissolved organic carbon concentrations, as well as decreases in metal concentrations. Additionally, these lakes are under the potential impacts of newly emerging environmental stressors such as climate warming and road salt contamination. Here, we revisited a suite of Sudbury-region lakes (n = 80) to examine the relationships between their current water chemistry and diatom assemblages preserved in surface sediments using a canonical correspondence analysis. Although the pH gradient in our study lakes is shorter (pH ~1.4) than in earlier calibration studies conducted in this region, lake water pH was still identified as the strongest environmental variable shaping diatom distributions and was used to construct a robust inference model (R 2 boot  = 0.73; RMSEP = 0.32). By assessing ecological changes experienced by a subset of these Sudbury-region lakes (n = 33) over the past few decades, we identified two major trends: an overall increase in diatom-inferred pH and a rise in the relative abundance of planktonic taxa. Our study provides useful insights into the autecology of major diatom taxa in acidified waters and highlights the importance of considering other anthropogenic stressors when assessing the recovery response of acid-impacted systems., (© 2022 Phycological Society of America.)

The programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is a potent inhibitory pathway involved in immune regulation and is a potential therapeutic target in transplantation. In this study, we show that overexpression of PD-1 on T cells (PD-1 Tg) promotes allograft tolerance in a fully MHC-mismatched cardiac transplant model when combined with costimulation blockade with CTLA-4-Ig. PD-1 overexpression on T cells also protected against chronic rejection in a single MHC II-mismatched cardiac transplant model, whereas the overexpression still allowed the generation of an effective immune response against an influenza A virus. Notably, Tregs from PD-1 Tg mice were required for tolerance induction and presented greater ICOS expression than those from WT mice. The survival benefit of PD-1 Tg recipients required ICOS signaling and donor PD-L1 expression. These results indicate that modulation of PD-1 expression, in combination with a costimulation blockade, is a promising therapeutic target to promote transplant tolerance.

Winter conditions, such as ice cover and snow accumulation, are changing rapidly at northern latitudes and can have important implications for lake processes. For example, snowmelt in the watershed-a defining feature of lake hydrology because it delivers a large portion of annual nutrient inputs-is becoming earlier. Consequently, earlier and a shorter duration of snowmelt are expected to affect annual phytoplankton biomass. To test this hypothesis, we developed an index of runoff timing based on the date when 50% of cumulative runoff between January 1 and May 31 had occurred. The runoff index was computed using stream discharge for inflows, outflows, or for flows from nearby streams for 41 lakes in Europe and North America. The runoff index was then compared with summer chlorophyll-a (Chl-a) concentration (a proxy for phytoplankton biomass) across 5-53 years for each lake. Earlier runoff generally corresponded to lower summer Chl-a. Furthermore, years with earlier runoff also had lower winter/spring runoff magnitude, more protracted runoff, and earlier ice-out. We examined several lake characteristics that may regulate the strength of the relationship between runoff timing and summer Chl-a concentrations; however, our tested covariates had little effect on the relationship. Date of ice-out was not clearly related to summer Chl-a concentrations. Our results indicate that ongoing changes in winter conditions may have important consequences for summer phytoplankton biomass and production., (© 2021 John Wiley & Sons Ltd.)

Surface water browning, the result of increasing concentrations of dissolved organic matter (DOM), has been widespread in northern ecosystems in recent decades. Here, we assess a database of 426 undisturbed headwater lakes and streams in Europe and North America for evidence of trends in DOM between 1990 and 2016. We describe contrasting changes in DOM trends in Europe (decelerating) and North America (accelerating), which are consistent with organic matter solubility responses to declines in sulfate deposition. While earlier trends (1990-2004) were almost entirely related to changes in atmospheric chemistry, climatic and chemical drivers were equally important in explaining recent DOM trends (2002-2016). We estimate that riverine DOM export from northern ecosystems increased by 27% during the study period. Increased summer precipitation strengthened upward dissolved organic carbon trends while warming apparently damped browning. Our results suggest strong but changing influences of air quality and climate on the terrestrial carbon cycle, and on the magnitude of carbon export from land to water.

Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change., (© 2021. The Author(s).)

The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity 1,2 , nutrient biogeochemistry 3 , greenhouse gas emissions 4 , and the quality of drinking water 5 . The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity 6,7 , but little is known about the changes in dissolved oxygen concentrations in lakes. Although the solubility of dissolved oxygen decreases with increasing water temperatures, long-term lake trajectories are difficult to predict. Oxygen losses in warming lakes may be amplified by enhanced decomposition and stronger thermal stratification 8,9 or oxygen may increase as a result of enhanced primary production 10 . Here we analyse a combined total of 45,148 dissolved oxygen and temperature profiles and calculate trends for 393 temperate lakes that span 1941 to 2017. We find that a decline in dissolved oxygen is widespread in surface and deep-water habitats. The decline in surface waters is primarily associated with reduced solubility under warmer water temperatures, although dissolved oxygen in surface waters increased in a subset of highly productive warming lakes, probably owing to increasing production of phytoplankton. By contrast, the decline in deep waters is associated with stronger thermal stratification and loss of water clarity, but not with changes in gas solubility. Our results suggest that climate change and declining water clarity have altered the physical and chemical environment of lakes. Declines in dissolved oxygen in freshwater are 2.75 to 9.3 times greater than observed in the world's oceans 6,7 and could threaten essential lake ecosystem services 2,3,5,11 .

The spiny water flea ( Bythotrephes cederströmii ), a freshwater crustacean considered to be the world's best-studied invasive zooplankter, was first recorded in North America in the Laurentian Great Lakes during the 1980s. Its arrival is widely considered to be the result of ocean-going cargo ships that translocated contaminated ballast water from Eurasia to the Great Lakes during the 1970-1980s. The subsequent first discovery of the species in inland lakes is consistent with the hypothesis that propagules dispersed initially from established Great Lakes populations. Here we present evidence of exoskeletal remains, including mandibles, tail spines, and resting eggs, in 210 Pb-dated lake sediment cores, which suggests that B. cederströmii was already resident in four inland North American lakes (two in Minnesota, USA; two in Ontario, Canada) by at least the early 1900s. Densities of exoskeletal remains were low and relatively steady from first appearance until about 1990, after which time they increased in all cores. The earliest evidence that we found was a mandible at 33-cm depth (pre-1650) in the sediments of Three Mile Lake, Ontario, Canada. These unexpected findings challenge the current paradigm of B. cederströmii invasion, renew uncertainty about the timing and sequence of its colonization of North American lakes, and potentially question our ability to detect invasive species with traditional sampling methods. We attempted to eliminate errors in the dated stratigraphies of the exoskeletal remains that might have been introduced either methodologically (e.g., core-wall smearing) or naturally (e.g., bioturbation). Nonetheless, given the very low numbers of subfossils encountered, questions remain about the possible artifactual nature of our observations and therefore we regard our results as 'preliminary findings' at this time., (© The Author(s) 2021.)

Plant flammability varies across species, but the evolutionary basis for this variation is not well understood. Phylogenetic analysis of interspecific variation in flammability can provide insights into the evolution of plant flammability. We measured four components of flammability (ignitability, sustainability, combustibility and consumability) to assess the shoot-level flammability of 21 species of Dracophyllum (Ericaceae). Using a macroevolutionary approach, we explored phylogenetic patterns of variation in shoot-level flammability. Shoot-level flammability varied widely in Dracophyllum. Species in the subgenus Oreothamnus had higher flammability and smaller leaves than those in the subgenus Dracophyllum. Shoot flammability (ignitability, combustibility and consumability) and leaf length showed phylogenetic conservatism across genus Dracophyllum, but exhibited lability among some closely related species, such as D. menziesii and D. fiordense. Shoot flammability of Dracophyllum species was negatively correlated with leaf length and shoot moisture content, but had no relationship with the geographic distribution of Dracophyllum species. Shoot-level flammability varied widely in the genus Dracophyllum, but showed phylogenetic conservatism. The higher flammability of the subgenus Oreothamnus may be an incidental or emergent property as a result of the evolution of flammability-related traits, such as smaller leaves, which were selected for other functions and incidentally changed flammability., (© 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.)

Widespread use of NaCl for road deicing has caused increased chloride concentrations in lakes near urban centers and areas of high road density. Chloride can be toxic, and water quality guidelines have been created to regulate it and protect aquatic life. However, these guidelines may not adequately protect organisms in low-nutrient, soft water lakes such as those underlain by the Precambrian Shield. We tested this hypothesis by conducting laboratory experiments on six Daphnia species using a soft water culture medium. We also examined temporal changes in cladoceran assemblages in the sediments of two small lakes on the Canadian Shield: one near a highway and the other >3 km from roads where salt is applied in the winter. Our results showed that Daphnia were sensitive to low chloride concentrations with decreased reproduction and increased mortality occurring between 5 and 40 mg Cl - /L. Analysis of cladoceran remains in lake sediments revealed changes in assemblage composition that coincided with the initial application of road salt in this region. In contrast, there were no changes detected in the remote lake. We found that 22.7% of recreational lakes in Ontario have chloride concentrations between 5 and 40 mg/L suggesting that cladoceran zooplankton in these lakes may already be experiencing negative effects of chloride.

Long-term patterns in dissolved organic carbon (DOC) concentrations in 49 eastern Canadian lakes from four sites were re-examined with a ~ 35-year (~1980-2015) dataset. The study sites were Dorset (number of lakes, n = 8), Experimental Lakes Area (ELA, n = 4), Kejimkujik (n = 26) and Yarmouth (n = 11). Lake DOC patterns were synchronous within each site. However, comparisons of DOC patterns across sites showed that they were synchronous only between the Kejimkujik and Yarmouth locations. Hence, these two sites were pooled into a single Nova Scotia site (NS). Increases in DOC concentration were evident in Dorset, Ontario from 1988 (r 2  = 0.78, p < 0.001) and NS from 2000 (r 2  = 0.43, p = 0.006). DOC at the ELA in northwestern Ontario had a different pattern compared to the other sites, i.e., DOC had increased earlier (1983-2000), and then, unlike Dorset and NS, neither an increase nor decrease was detected between 2001 and 2015 (p = 0.78). Precipitation and sulfur deposition explained the greatest variance in DOC patterns at the Dorset and NS sites (i.e., precipitation: 21-49% and sulfur deposition: 24-54%). Precipitation was the most important driver of DOC at the ELA. Our results indicate that all the sites have gone through a process of increasing DOC, but at different times. The stabilizing pattern at the ELA since 2001 may suggest that DOC concentrations in ELA lakes have reached, or are approaching a new equilibrium, a phenomenon that was not observed at the other sites. Also, the increase in DOC was not always associated with declining sulfur deposition (e.g., ELA). Therefore, we conclude that there was considerable variation in DOC patterns across this large geographic region of Canada and potential drivers of these patterns were not consistent across these diverse sites., 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., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Since the implementation of large-scale lake monitoring in the ~1980s, water color and dissolved organic carbon (DOC) concentrations have increased in many northern lakes (i.e., lake browning), impacting the functioning of aquatic ecosystems. In regions that formerly experienced high levels of acid deposition, this browning trend has been largely attributed to the recovery from the impacts of past acid deposition. However, the extent to which DOC levels have now returned to naturally higher, pre-industrial conditions is still poorly understood. In this study, we assessed whether DOC levels are still influenced by acid deposition in lakes near Sudbury, Ontario, a region that has been heavily affected by sulfur dioxide emissions from local metal smelting during the 20th century. We analyzed water chemistry monitoring data (1981-2018), together with comparisons between modern and pre-industrial DOC levels inferred from sediment spectroscopy, for 51 acid-sensitive and 24 buffered reference lakes across the Sudbury landscape. Since 1981, DOC concentrations doubled in acid-sensitive lakes, with a mean increase of +1.6 mg/L, whereas in more buffered reference lakes, mean DOC levels increased by only 0.8 mg/L. Similarly, sediment-inferred DOC trends indicate that current DOC levels are, on average, ~22% below pre-industrial levels in acid sensitive systems compared to only ~10% in buffered lakes. Weakening correlations between DOC and acidification-related water chemistry variables (e.g., pH, alkalinity, metals) further indicate a diminishing influence of acid deposition on DOC in Sudbury lakes. These results highlight the strong impact that acid deposition has historically had on lake-water DOC dynamics in this region, but also suggest that DOC levels are approaching natural baseline levels in less acid-sensitive lakes, and that other drivers, such as changes in climate or vegetation cover, are now becoming the dominant controls on changes in DOC concentrations., 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 © 2020 Elsevier B.V. All rights reserved.)

The common brushtail possum ( Trichosurus vulpecula ), introduced from Australia in the mid-nineteenth century, is an invasive species in New Zealand where it is widespread and forms the largest self-sustained reservoir of bovine tuberculosis ( Mycobacterium bovis ) among wild populations. Conservation and agricultural authorities regularly apply a series of population control measures to suppress brushtail possum populations. The evolutionary consequence of more than half a century of intensive population control operations on the species' genomic diversity and population structure is hindered by a paucity of available genomic resources. This study is the first to characterise the functional content and diversity of brushtail possum liver and brain cerebral cortex transcriptomes. Raw sequences from hepatic cells and cerebral cortex were assembled into 58,001 and 64,735 transcripts respectively. Functional annotation and polymorphism assignment of the assembled transcripts demonstrated a considerable level of variation in the core metabolic pathways that represent potential targets for selection pressure exerted by chemical toxicants. This study suggests that the brushtail possum population in New Zealand harbours considerable variation in metabolic pathways that could potentially promote the development of tolerance against chemical toxicants.

Terrestrial plants and fire have interacted for at least 420 million years 1 . Whether recurrent fire drives plants to evolve higher flammability and what the evolutionary pattern of plant flammability is remain unclear 2-7 . Here, we show that phylogeny, the susceptibility of a habitat to have recurrent fires (that is, fire-proneness) and growth form are important predictors of the shoot flammability of 194 indigenous and introduced vascular plant species (Tracheophyta) from New Zealand. The phylogenetic signal of the flammability components and the variation in flammability among phylogenetic groups (families and higher taxonomic level clades) demonstrate that shoot flammability is phylogenetically conserved. Some closely related species, such as in Dracophyllum (Ericaceae), vary in flammability, indicating that flammability exhibits evolutionary flexibility. Species in fire-prone ecosystems tend to be more flammable than species from non-fire-prone ecosystems, suggesting that fire may have an important role in the evolution of plant flammability. Growth form also influenced flammability-forbs were less flammable than grasses, trees and shrubs; by contrast, grasses had higher biomass consumption by fire than other groups. The results show that shoot flammability of plants is largely correlated with phylogenetic relatedness, and high flammability may result in parallel evolution driven by environmental factors, such as fire regime.

Background: CD47 is a broadly expressed cell surface glycoprotein associated with immune evasion. Interaction with the inhibitory receptor signal regulatory protein alpha (SIRPα), primarily expressed on myeloid cells, normally serves to restrict effector function (eg, phagocytosis and immune cell homeostasis). CD47/SIRPα antagonists, commonly referred to as 'macrophage checkpoint' inhibitors, are being developed as cancer interventions. SRF231 is an investigational fully human IgG 4 anti-CD47 antibody that is currently under evaluation in a phase 1 clinical trial. The development and preclinical characterization of SRF231 are reported here., Methods: SRF231 was characterized in assays designed to probe CD47/SIRPα blocking potential and effects on red blood cell (RBC) phagocytosis and agglutination. Additionally, SRF231-mediated phagocytosis and cell death were assessed in macrophage:tumor cell in vitro coculture systems. Further mechanistic studies were conducted within these coculture systems to ascertain the dependency of SRF231-mediated antitumor activity on Fc receptor engagement vs CD47/SIRPα blockade. In vivo, SRF231 was evaluated in a variety of hematologic xenograft models, and the mechanism of antitumor activity was assessed using cytokine and macrophage infiltration analyses following SRF231 treatment., Results: SRF231 binds CD47 and disrupts the CD47/SIRPα interaction without causing hemagglutination or RBC phagocytosis. SRF231 exerts antitumor activity in vitro through both phagocytosis and cell death in a manner dependent on the activating Fc-gamma receptor (FcγR), CD32a. Through its Fc domain, SRF231 engagement with macrophage-derived CD32a serves dual purposes by eliciting FcγR-mediated phagocytosis of cancer cells and acting as a scaffold to drive CD47-mediated death signaling into tumor cells. Robust antitumor activity occurs across multiple hematologic xenograft models either as a single agent or in combination with rituximab. In tumor-bearing mice, SRF231 increases tumor macrophage infiltration and induction of the macrophage cytokines, mouse chemoattractant protein 1 and macrophage inflammatory protein 1 alpha. Macrophage depletion results in diminished SRF231 antitumor activity, underscoring a mechanistic role for macrophage engagement by SRF231., Conclusion: SRF231 elicits antitumor activity via apoptosis and phagocytosis involving macrophage engagement in a manner dependent on the FcγR, CD32a., Competing Interests: Competing interests: All authors are current or former employees and shareholders of Surface Oncology., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Dissolved organic carbon (DOC) concentrations and water colour are increasing in many inland waters across northern Europe and northeastern North America. This inland-water "browning" has profound physical, chemical and biological repercussions for aquatic ecosystems affecting water quality, biological community structures and aquatic productivity. Potential drivers of this "browning" trend are complex and include reductions in atmospheric acid deposition, changes in land use/cover, increased nitrogen deposition and climate change. However, because of the overlapping impacts of these stressors, their relative contributions to DOC dynamics remain unclear, and without appropriate long-term monitoring data, it has not been possible to determine whether the ongoing "browning" is unprecedented or simply a "re-browning" to pre-industrial DOC levels. Here, we demonstrate the long-term impacts of acid deposition and climate change on lake-water DOC concentrations in low and high acid-deposition areas using infrared spectroscopic techniques on ~200-year-long lake-sediment records from central Canada. We show that acid deposition suppressed naturally higher DOC concentrations during the 20th century, but that a "re-browning" of lakes is now occurring with emissions reductions in formerly high deposition areas. In contrast, in low deposition areas, climate change is forcing lakes towards new ecological states, as lake-water DOC concentrations now often exceed pre-industrial levels.

We deploy camera traps to monitor feral cat ( Felis catus ) populations at two pastoral sites in Hawke's Bay, North Island, New Zealand. At Site 1, cameras are deployed at pre-determined GPS points on a 500-m grid, and at Site 2, cameras are strategically deployed with a bias towards forest and forest margin habitat where possible. A portion of cameras are also deployed in open farmland habitat and mixed scrub. We then use the abundance-induced heterogeneity Royle-Nichols model to estimate mean animal abundance and detection probabilities for cameras in each habitat type. Model selection suggests that only cat abundance varies by habitat type. Mean cat abundance is highest at forest margin cameras for both deployment methods (3 cats [95% CI 1.9-4.5] Site 1, and 1.7 cats [95% CI 1.2-2.4] Site 2) but not substantially higher than in forest habitats (1.7 cats [95% CI 0.8-3.6] Site 1, and 1.5 cats [95% CI 1.1-2.0] Site 2). Model selection shows detection probabilities do not vary substantially by habitat (although they are also higher for cameras in forest margins and forest habitats) and are similar between sites (8.6% [95% CI 5.4-13.4] Site 1, and 8.3% [5.8-11.9] Site 2). Cat detections by camera traps are higher when placed in forests and forest margins; thus, strategic placement may be preferable when monitoring feral cats in a pastoral landscape.

Calcium (Ca) is an essential element for almost all living organisms. Here, we examined global variation and controls of freshwater Ca concentrations, using 440 599 water samples from 43 184 inland water sites in 57 countries. We found that the global median Ca concentration was 4.0 mg L -1 with 20.7% of the water samples showing Ca concentrations ≤ 1.5 mg L -1 , a threshold considered critical for the survival of many Ca-demanding organisms. Spatially, freshwater Ca concentrations were strongly and proportionally linked to carbonate alkalinity, with the highest Ca and carbonate alkalinity in waters with a pH around 8.0 and decreasing in concentrations towards lower pH. However, on a temporal scale, by analyzing decadal trends in >200 water bodies since the 1980s, we observed a frequent decoupling between carbonate alkalinity and Ca concentrations, which we attributed mainly to the influence of anthropogenic acid deposition. As acid deposition has been ameliorated, in many freshwaters carbonate alkalinity concentrations have increased or remained constant, while Ca concentrations have rapidly declined towards or even below pre-industrial conditions as a consequence of recovery from anthropogenic acidification. Thus, a paradoxical outcome of the successful remediation of acid deposition is a globally widespread freshwater Ca concentration decline towards critically low levels for many aquatic organisms.

Despite being classified as critically endangered, little work has been done on leopard protection in Pakistan. Once widely present throughout this region, leopards are now sparsely distributed, and possibly extinct from much of their previously recorded habitat. While leopards show morphological and genetic variation across their species range worldwide, resulting in the classification of nine different subspecies, the leopard genetic structure across Pakistan is unknown, with previous studies including only a very limited sampling. To clarify the genetic status of leopards in Pakistan we investigated the sequence variation in the subunit 5 of the mitochondrial gene NADH from 43 tissue samples and compared it with 238 sequences available from online databases. Phylogenetic analysis clearly separates the Pakistani leopards from the African and Arabian clades, confirming that leopards from Pakistan are members of the Asian clade. Furthermore, we identified two separate subspecies haplotypes within our dataset: P. p. fusca ( N  = 23) and P. p. saxicolor ( N  = 12)., Competing Interests: The authors declare there are no competing interests.

Wildfire is a widespread natural hazard that is expected to increase in areal extent, severity and frequency with ongoing changes in climate and land-use. One tool that has been used in an effort to reduce the damage caused by wildfires is green firebreaks: strips of low-flammability vegetation grown at strategic locations in the landscape. Green firebreaks are increasingly being recommended for wildfire management and have been implemented in many countries. The approach is particularly widely used in China, where more than 364,000 km of green firebreaks have been planted and a further 167,000 km are planned for construction before 2025. China is not only a world leader in the implementation of green firebreaks but has also led the way in testing the effectiveness of green firebreaks and in providing guidelines for green firebreak construction. However, most of this research has been reported in the non-English literature, and so is inaccessible to many readers. Here we review the extensive research on the construction and effectiveness of green firebreaks in China and examine how the lessons learned from this research could contribute to the effective implementation of green firebreaks globally. Chinese studies suggest that the ideal species for green firebreaks should meet trait requirements from three perspectives: ecological, silvicultural and economic. Green firebreaks with a multi-layered structure and a closed canopy have the potential to be an effective, long-term, biodiversity-friendly and low-cost tool for fire suppression, although they complement rather than replace other more traditional fire suppression approaches., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Formerly acidified lakes and watersheds can become more productive when recovering from acidity, especially when exposed to anthropogenic disturbance and increased nutrient loading. Occasional toxic cyanobacterial blooms and other signs of eutrophication have been observed for a decade in lakes located in the Sudbury, Ontario, mining area that was severely affected by acid deposition before the start of smelter emission reductions in the 1970s. Oligotrophic Long Lake and its upstream lakes have been exposed to waste water input and development impacts from the City of Greater Sudbury and likely have a legacy of nutrient enrichment in their sediment. Based on observations from other published studies, we hypothesized that P, which was previously adsorbed by metals liberated during acidification caused by the mining activities, is now being released from the sediment as internal P loading contributing to increased cyanobacteria biomass. Support for this hypothesis includes (1) lake observations of oxygen depletion and hypolimnetic anoxia and slightly elevated hypolimnetic total P concentration and (2) P, Al, and Fe fractionation of two sediment layers (0-5, 5-10 cm), showing elevated concentrations of TP and iron releasable P (BD-fraction), decreased concentrations in fractions associated with Al, and fraction ratios indicating decreased sediment adsorption capacity. The comparison with two moderately enriched lakes within 200 km distance, but never directly affected by mining operations, supports the increasing similarity of Long Lake surficial sediment adsorption capacity with that of unaffected lakes. There is cause for concern that increased eutrophication including the proliferation of cyanobacteria of formerly acidic lakes is wide-spread and occurs wherever recovery coincides with anthropogenic disturbances and physical changes related to climate change., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The New Zealand fur seal (Arctocephalus forsteri) passed through a population bottleneck due to commercial sealing during the eighteenth to nineteenth centuries. To facilitate future management options, we reconstructed the demographic history of New Zealand fur seals in a Bayesian framework using maternally inherited, mitochondrial DNA sequences. Mitogenomic data suggested two separate clades (most recent common ancestor 5000 years ago) of New Zealand fur seals that survived large-scale human harvest. Mitochondrial haplotype diversity was high, with 45 singletons identified from 46 individuals although mean nucleotide diversity was low (0.012 ± 0.0061). Variation was not constrained geographically. Analyses of mitogenomes support the hypothesis for a population bottleneck approximately 35 generations ago, which coincides with the peak of commercial sealing. Mitogenomic data are consistent with a pre-human effective population size of approximately 30,000 that first declined to around 10,000 (due to the impact of Polynesian colonization, particularly in the first 100 years of their arrival into New Zealand), and then to 100-200 breeding individuals during peak of commercial sealing.

Changing lake water total organic carbon (TOC) concentrations are of concern for lake management because of corresponding effects on aquatic ecosystem functioning, drinking water resources and carbon cycling between land and sea. Understanding the importance of human activities on TOC changes requires knowledge of past concentrations; however, water-monitoring data are typically only available for the past few decades, if at all. Here, we present a universal model to infer past lake water TOC concentrations in northern lakes across Europe and North America that uses visible-near-infrared (VNIR) spectroscopy on lake sediments. In the orthogonal partial least-squares model, VNIR spectra of surface-sediment samples are calibrated against corresponding surface water TOC concentrations (0.5-41 mg L -1 ) from 345 Arctic to northern temperate lakes in Canada, Greenland, Sweden and Finland. Internal model-cross-validation resulted in a R 2 of 0.57 and a prediction error of 4.4 mg TOC L -1 . First applications to lakes in southern Ontario and Scotland, which are outside of the model's geographic range, show the model accurately captures monitoring trends, and suggests that TOC dynamics during the 20th century at these sites were primarily driven by changes in atmospheric deposition. Our results demonstrate that the lake water TOC model has multiregional applications and is not biased by postdepositional diagenesis, allowing the identification of past TOC variations in northern lakes of Europe and North America over time scales of decades to millennia.

Rheumatoid arthritis is a chronic disease affecting the joints. Treatment can include immobilisation of the affected joint with a custom-fitting splint, which is typically fabricated by hand from low temperature thermoplastic, but the approach poses several limitations. This study focused on the evaluation, by finite element analysis, of additive manufacturing techniques for wrist splints in order to improve upon the typical splinting approach. An additive manufactured/3D printed splint, specifically designed to be built using Objet Connex multi-material technology and a virtual model of a typical splint, digitised from a real patient-specific splint using three-dimensional scanning, were modelled in computer-aided design software. Forty finite element analysis simulations were performed in flexion-extension and radial-ulnar wrist movements to compare the displacements and the stresses. Simulations have shown that for low severity loads, the additive manufacturing splint has 25%, 76% and 27% less displacement in the main loading direction than the typical splint in flexion, extension and radial, respectively, while ulnar values were 75% lower in the traditional splint. For higher severity loads, the flexion and extension movements resulted in deflections that were 24% and 60%, respectively, lower in the additive manufacturing splint. However, for higher severity loading, the radial defection values were very similar in both splints and ulnar movement deflection was higher in the additive manufacturing splint. A physical prototype of the additive manufacturing splint was also manufactured and was tested under normal conditions to validate the finite element analysis data. Results from static tests showed maximum displacements of 3.46, 0.97, 3.53 and 2.51 mm flexion, extension, radial and ulnar directions, respectively. According to these results, the present research argues that from a technical point of view, the additive manufacturing splint design stands at the same or even better level of performance in displacements and stress values in comparison to the typical low temperature thermoplastic approach and is therefore a feasible approach to splint design and manufacture.

The complete mitochondrial genome of three mustelid species, stoats (Mustela erminea), weasels (Mustela nivalis) and ferrets (Mustela furo), and the New Zealand fur seal (Arctocephalus forsteri) were sequenced using direct mitochondrial DNA extraction and overlapping long PCRs. The usual 37 mammalian mitochondrial genes (13 protein coding genes, 22 t-RNA and 2 r-RNA) were identified in all four mitogenomes. The divergence of stoats from other members of the sub-family Mustelinae was dated 4.5 million years ago. The mitogenomic data were consistent with a bear-like origin of seals.

A recent rise in the relative abundance of Discostella species (D. stelligera and D. pseudostelligera) has been well documented from sedimentary diatom assemblages across the Northern Hemisphere. This unprecedented change over the last ~150 years has been linked to rises in atmospheric temperatures, changes in ice cover, and/or increases in thermal stability, among other factors. The bi-weekly monitoring data from two boreal lakes at the Experimental Lakes Area (ELA) in northwestern Ontario were analyzed across seasons (spring, summer, and fall) and decades (1970s-2000s). We found that Discostella species are primarily spring/early summer bloomers (i.e., late April to June) in these lakes and changes in concentrations of Discostella over time were most pronounced in the spring or early summer months. Increases in Discostella abundance over time may be linked to earlier ice-off and a longer period of spring turnover, resulting from increased winter and spring temperatures. It is also possible that a trophic mismatch between the spring diatom bloom and zooplankton is occurring, thus reducing diatom loss rates, and resulting in greater overall abundance. Moreover, the spring dominance of Discostella in our study lakes occurred at a time of the year when nutrient concentrations were at their highest seasonally, suggesting that these taxa are neither limited directly by nutrients, nor responding to enhanced stratification during the summer months in these lakes., (© 2016 Phycological Society of America.)

Mercury (Hg) is an anthropogenic pollutant that is toxic to wildlife and humans, but the response of remote ecosystems to globally distributed Hg is elusive. Here, we use DNA extracted from a dated sediment core to infer the response of microbes to historical Hg delivery. We observe a significant association between the mercuric reductase gene (merA) phylogeny and the timing of Hg deposition. Using relaxed molecular clock models, we show a significant increase in the scaled effective population size of the merA gene beginning ~200 years ago, coinciding with the Industrial Revolution and a coincident strong signal for positive selection acting on residues in the terminal region of the mercuric reductase. This rapid evolutionary response of microbes to changes in the delivery of anthropogenic Hg indicates that microbial genomes record ecosystem response to pollutant deposition in remote regions.

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential negative regulator of T cell responses. Germline Ctla4 deficiency is lethal, making investigation of the function of CTLA-4 on mature T cells challenging. To elucidate the function of CTLA-4 on mature T cells, we have conditionally ablated Ctla4 in adult mice. We show that, in contrast to germline knockout mice, deletion of Ctla4 during adulthood does not precipitate systemic autoimmunity, but surprisingly confers protection from experimental autoimmune encephalomyelitis (EAE) and does not lead to increased resistance to MC38 tumors. Deletion of Ctla4 during adulthood was accompanied by activation and expansion of both conventional CD4(+)Foxp3(-) (T conv) and regulatory Foxp3(+) (T reg cells) T cell subsets; however, deletion of CTLA-4 on T reg cells was necessary and sufficient for protection from EAE. CTLA-4 deleted T reg cells remained functionally suppressive. Deletion of Ctla4 on T reg cells alone or on all adult T cells led to major changes in the Ctla4 sufficient T conv cell compartment, including up-regulation of immunoinhibitory molecules IL-10, LAG-3 and PD-1, thereby providing a compensatory immunosuppressive mechanism. Collectively, our findings point to a profound role for CTLA-4 on T reg cells in limiting their peripheral expansion and activation, thereby regulating the phenotype and function of T conv cells., (© 2015 Paterson et al.)

The balance between Th17 and T regulatory (Treg) cells critically modulates immune homeostasis, with an inadequate Treg response contributing to inflammatory disease. Using an unbiased chemical biology approach, we identified a novel role for the dual specificity tyrosine-phosphorylation-regulated kinase DYRK1A in regulating this balance. Inhibition of DYRK1A enhances Treg differentiation and impairs Th17 differentiation without affecting known pathways of Treg/Th17 differentiation. Thus, DYRK1A represents a novel mechanistic node at the branch point between commitment to either Treg or Th17 lineages. Importantly, both Treg cells generated using the DYRK1A inhibitor harmine and direct administration of harmine itself potently attenuate inflammation in multiple experimental models of systemic autoimmunity and mucosal inflammation. Our results identify DYRK1A as a physiologically relevant regulator of Treg cell differentiation and suggest a broader role for other DYRK family members in immune homeostasis. These results are discussed in the context of human diseases associated with dysregulated DYRK activity.

Background: Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface., Methods: From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists., Findings: The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists., Interpretation: Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of throughput requiring human input.