Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.

In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin ß1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.

Transient social-ecological dynamics reveal signals of decoupling in a highly disturbed Anthropocene landscape.

Understanding the transient dynamics of interlinked social-ecological systems (SES) is imperative for assessing sustainability in the Anthropocene. However, how to identify critical transitions in real-world SES remains a formidable challenge. In this study, we present an evolutionary framework to characterize these dynamics over an extended historical timeline. Our approach leverages multidecadal rates of change in socioeconomic data, paleoenvironmental, and cutting-edge sedimentary ancient DNA records from China's Yangtze River Delta, one of the most densely populated and intensively modified landscapes on Earth. Our analysis reveals two significant social-ecological transitions characterized by contrasting interactions and feedback spanning several centuries. Initially, the regional SES exhibited a loosely connected and ecologically sustainable regime. Nevertheless, starting in the 1950s, an increasingly interconnected regime emerged, ultimately resulting in the crossing of tipping points and an unprecedented acceleration in soil erosion, water eutrophication, and ecosystem degradation. Remarkably, the second transition occurring around the 2000s, featured a notable decoupling of socioeconomic development from ecoenvironmental degradation. This decoupling phenomenon signifies a more desirable reconfiguration of the regional SES, furnishing essential insights not only for the Yangtze River Basin but also for regions worldwide grappling with similar sustainability challenges. Our extensive multidecadal empirical investigation underscores the value of coevolutionary approaches in understanding and addressing social-ecological system dynamics.

Characterization of lacustrine harmful algal blooms using multiple biomarkers: Historical processes, driving synergy, and ecological shifts.

Harmful algal blooms (HABs) producing toxic metabolites are increasingly threatening environmental and human health worldwide. Unfortunately, long-term process and mechanism triggering HABs remain largely unclear due to the scarcity of temporal monitoring. Retrospective analysis of sedimentary biomarkers using up-to-date chromatography and mass spectrometry techniques provide a potential means to reconstruct the past occurrence of HABs. By combining aliphatic hydrocarbons, photosynthetic pigments, and cyanotoxins, we quantified herein century-long changes in abundance, composition, and variability of phototrophs, particularly toxigenic algal blooms, in China's third largest freshwater Lake Taihu. Our multi-proxy limnological reconstruction revealed an abrupt ecological shift in the 1980s characterized by elevated primary production, Microcystis-dominated cyanobacterial blooms, and exponential microcystin production, in response to nutrient enrichment, climate change, and trophic cascades. The empirical results from ordination analysis and generalized additive models support climate warming and eutrophication synergy through nutrient recycling and their feedback through buoyant cyanobacterial proliferation, which sustain bloom-forming potential and further promote the occurrence of increasingly-toxic cyanotoxins (e.g., microcystin-LR) in Lake Taihu. Moreover, temporal variability of the lake ecosystem quantified using variance and rate of change metrics rose continuously after state change, indicating increased ecological vulnerability and declined resilience following blooms and warming. With the persistent legacy effects of lake eutrophication, nutrient reduction efforts mitigating toxic HABs probably be overwhelmed by climate change effects, emphasizing the need for more aggressive and integrated environmental strategies.

In flux: Annual transport and deposition of suspended heavy metals and trace elements in the urbanised, tropical Red River Delta, Vietnam.

Due to the depositional environment, river deltas are said to act as filters and sinks for pollutants. However, many deltas are also densely populated and rapidly urbanizing, creating new and increased sources of pollutants. These sources pose the risk of tipping these environments from pollution sinks to sources, to the world's oceans. We provide detailed seasonal and annual assessments of metal contaminants in riverine suspended particulate matter (SPM) across the densely populated Red River Delta (RRD), Vietnam. The global contributions of elements from the RRD are all <0.2% with many elemental fluxes <0.01%, suggesting the RRD is not a major source of elemental pollution to the ocean. However, 'hotspots' of metal pollution due to human activity and the impacts of tropical storm Son Tinh (July 2018) exceed both national level regulations and international measures of toxicity (e.g. enrichment factors). There is widespread 'extreme pollution' of Cd (enrichment factor >40) and concentrations of As higher than national regulation limits (>17 mg/Kg) at all sites other than one upstream, agricultural-dominated tributary in the dry season. These 'hotspots' are characterised by high inputs of organic matter (e.g. manure fertiliser and urban wastewater), which influences elemental mobility in the particulate and dissolved phases, and are potentially significant sources of pollution downstream. In addition, in the marine and fresh water mixing zone, salinity effects metal complexation with organic matter increasing metals in the particulate phase. Our calculations indicate that the delta is currently acting as a pollutant sink (as determined by high levels of pollutant deposition ∼50%). However, increased in-washing of pollutants and future projected increases in monsoon intensity, saline intrusion, and human activity could shift the delta to become a source of toxic metals. We show the importance of monitoring environmental parameters (primarily dissolved organic matter and salinity) in the RRD to assess the risk of transport and accumulation of toxic metals in the delta sediments, which can lead to net-increases in anthropogenic pollution in the coastal zone and the incorporation of toxic elements in the food chain.

Pollen-based reconstruction reveals the impact of the onset of agriculture on plant functional trait composition.

The onset of agriculture improved the capacity of ecosystems to produce food, but inadvertently altered other vital ecosystem functions. Plant traits play a central role in determining ecosystem properties, therefore we investigated how the onset of agriculture in Europe changed plant trait composition using 78 pollen records. Using a novel Bayesian approach for reconstructing plant trait composition from pollen records, we provide a robust method that can account for trait variability within pollen types. We estimate an overall four-fold decrease in plant size through agriculture and associated decreases in leaf and seed size. We show an increase in niche space towards the resource-acquisitive end of the leaf economic spectrum. Decreases in leaf phosphorus might have been caused by nutrient depletion through grazing and burning. Our results show that agriculture, from its start, has likely been gradually impacting biogeochemical cycles through altered vegetation composition.

Changing nutrient cycling in Lake Baikal, the world's oldest lake.

Lake Baikal, lying in a rift zone in southeastern Siberia, is the world's oldest, deepest, and most voluminous lake that began to form over 30 million years ago. Cited as the "most outstanding example of a freshwater ecosystem" and designated a World Heritage Site in 1996 due to its high level of endemicity, the lake and its ecosystem have become increasingly threatened by both climate change and anthropogenic disturbance. Here, we present a record of nutrient cycling in the lake, derived from the silicon isotope composition of diatoms, which dominate aquatic primary productivity. Using historical records from the region, we assess the extent to which natural and anthropogenic factors have altered biogeochemical cycling in the lake over the last 2,000 y. We show that rates of nutrient supply from deep waters to the photic zone have dramatically increased since the mid-19th century in response to changing wind dynamics, reduced ice cover, and their associated impact on limnological processes in the lake. With stressors linked to untreated sewage and catchment development also now impacting the near-shore region of Lake Baikal, the resilience of the lake's highly endemic ecosystem to ongoing and future disturbance is increasingly uncertain.

Diatom-based water-table reconstruction in Sphagnum peatlands of northeastern China.

Peatlands are important ecosystems for biodiversity conservation, global carbon cycling and water storage. Hydrological changes due to climate variability have accelerated the degradation of global and regional ecosystem services of peatlands. Diatoms are important producers and bioindicators in wetlands, but comprehensive diatom-based inference models for palaeoenvironmental reconstruction in peatlands are scarce. To explore the use of diatoms for investigating peatland hydrological change, this study established a training set consisting of diatom composition and twelve environmental factors from 105 surface samples collected from five Sphagnum peatlands in northeastern China. Diatom communities were dominated by Eunotia species. Ordination analyses showed that depth to the water table (DWT) was the most important factor influencing diatom distribution, independently accounting for 4.99% of total variance in diatom data. Accordingly, a diatom-based DWT transfer function was developed and thoroughly tested. The results revealed that the best-performing model was based on weighted averaging with inverse deshrinking (R2 = 0.66, RMSEP = 8.8 cm with leave-one-out cross validation). Quantitative reconstruction of DWT on a short peat core collected from the Aershan Peatland (Inner Mongolia) recorded climate-mediated hydrological changes over the last two centuries. This study presents the first diatom-water table transfer function in Sphagnum peatlands, and highlights the potential of diatoms as a powerful tool to assess the magnitude of past hydrological changes in peatlands of northeastern China, as well as similar peaty environments worldwide.

Admixture between Ancient Lineages, Selection, and the Formation of Sympatric Stickleback Species-Pairs.

Ecological speciation has become a popular model for the development and maintenance of reproductive isolation in closely related sympatric pairs of species or ecotypes. An implicit assumption has been that such pairs originate (possibly with gene flow) from a recent, genetically homogeneous ancestor. However, recent genomic data have revealed that currently sympatric taxa are often a result of secondary contact between ancestrally allopatric lineages. This has sparked an interest in the importance of initial hybridization upon secondary contact, with genomic reanalysis of classic examples of ecological speciation often implicating admixture in speciation. We describe a novel occurrence of unusually well-developed reproductive isolation in a model system for ecological speciation: the three-spined stickleback (Gasterosteus aculeatus), breeding sympatrically in multiple lagoons on the Scottish island of North Uist. Using morphological data, targeted genotyping, and genome-wide single-nucleotide polymorphism data, we show that lagoon resident and anadromous ecotypes are strongly reproductively isolated with an estimated hybridization rate of only ∼1%. We use palaeoecological and genetic data to test three hypotheses to explain the existence of these species-pairs. Our results suggest that recent, purely ecological speciation from a genetically homogeneous ancestor is probably not solely responsible for the evolution of species-pairs. Instead, we reveal a complex colonization history with multiple ancestral lineages contributing to the genetic composition of species-pairs, alongside strong disruptive selection. Our results imply a role for admixture upon secondary contact and are consistent with the recent suggestion that the genomic underpinning of ecological speciation often has an older, allopatric origin.

Correction: Diatom evidence of 20th century ecosystem change in Lake Baikal, Siberia.

[This corrects the article DOI: 10.1371/journal.pone.0208765.].

Diatom evidence of 20th century ecosystem change in Lake Baikal, Siberia.

Lake Baikal has been experiencing limnological changes from recent atmospheric warming since the 1950s, with rising lake water temperatures, reduced ice cover duration and reduced lake surface-water mixing due to stronger thermal stratification. This study uses lake sediment cores to reconstruct recent changes (c. past 20 years) in Lake Baikal's pelagic diatom communities relative to previous 20th century diatom assemblage records collected in 1993 and 1994 at the same locations in the lake. Recent changes documented within the core-top diatom records agree with predictions of diatom responses to warming at Lake Baikal. Sediments in the south basin of the lake exhibit clear temporal changes, with the most rapid occurring in the 1990's with shifts towards higher abundances of the cosmopolitan Synedra acus and a decline in endemic species, mainly Cyclotella minuta and Stephanodiscus meyerii and to a lesser extent Aulacoseira baicalensis and Aulacoseira skvortzowii. The north basin, in contrast, shows no evidence of recent diatom response to lake warming despite marked declines in north basin ice cover in recent decades. This study also shows no diatom-inferred evidence of eutrophication from deep water sediments. However, due to the localised impacts seen in areas of Lake Baikal's shoreline from nutrient pollution derived from inadequate sewage treatment, urgent action is vital to prevent anthropogenic pollution extending into the open waters.

Regional versus local drivers of water quality in the Windermere catchment, Lake District, United Kingdom: The dominant influence of wastewater pollution over the past 200 years.

Freshwater ecosystems are threatened by multiple anthropogenic stressors acting over different spatial and temporal scales, resulting in toxic algal blooms, reduced water quality and hypoxia. However, while catchment characteristics act as a 'filter' modifying lake response to disturbance, little is known of the relative importance of different drivers and possible differentiation in the response of upland remote lakes in comparison to lowland, impacted lakes. Moreover, many studies have focussed on single lakes rather than looking at responses across a set of individual, yet connected lake basins. Here we used sedimentary algal pigments as an index of changes in primary producer assemblages over the last ~200 years in a northern temperate watershed consisting of 11 upland and lowland lakes within the Lake District, United Kingdom, to test our hypotheses about landscape drivers. Specifically, we expected that the magnitude of change in phototrophic assemblages would be greatest in lowland rather than upland lakes due to more intensive human activities in the watersheds of the former (agriculture, urbanization). Regional parameters, such as climate dynamics, would be the predominant factors regulating lake primary producers in remote upland lakes and thus, synchronize the dynamic of primary producer assemblages in these basins. We found broad support for the hypotheses pertaining to lowland sites as wastewater treatment was the main predictor of changes to primary producer assemblages in lowland lakes. In contrast, upland headwaters responded weakly to variation in atmospheric temperature, and dynamics in primary producers across upland lakes were asynchronous. Collectively, these findings show that nutrient inputs from point sources overwhelm climatic controls of algae and nuisance cyanobacteria, but highlights that large-scale stressors do not always initiate coherent regional lake response. Furthermore, a lake's position in its landscape, its connectivity and proximity to point nutrients are important determinants of changes in production and composition of phototrophic assemblages.

Effects of dam construction and increasing pollutants on the ecohydrological evolution of a shallow freshwater lake in the Yangtze floodplain.

Large river-floodplain systems which provide a variety of societal, economic and biological benefits are undergoing extensive and intensive human disturbance. However, floodplain lakes responses to multiple stressors are poorly understood. The Yangtze River and its floodplain which provide water and food resources for more than 300 million people are an important region in China. Hydrological regulation as well as socio-economic development have brought profound negative influence on this ecologically important area. To improve understanding of decadal-scale responses of floodplain lakes to multiple stressors, lake sediment proxies including particle size, geochemical elements, diatoms and chironomids were analysed in a lead-210 dated core from Futou Lake. The analyses show that dams constructed in 1935 and the early 1970s stabilized hydrological conditions in Futou Lake and impeded the interaction with the Yangtze River, resulting in a decrease in major elements (e.g., Mg, Al, Fe) transported into the lake and an increase of macrophyte-related chironomids (C. sylvestris-type, P. penicillatus-type and Paratanytarsus sp.). After the late 1990s, further decreases in major elements and increases in median grain size are attributed to the erosion of the Yangtze riverbed and declining supply of major elements-enriched sediments from the upper Yangtze caused by the impoundment of the Three Gorges Dam. Chironomid and diatom assemblages indicate that hydrological stabilization caused by dam constructions stimulated the growth of macrophytes, which may be important in buffering against an ecosystem state change towards a phytoplankton-dominated and turbid state with ongoing eutrophication. However, a recent increase in Zn, TP and the emergence of eutrophic diatom and chironomid species indicate initial signs of water quality deterioration which may be related to the combined effects of hydrological stabilization and aquaculture. Over all, the sediment record from Futou Lake emphasizes the importance of interactions between hydrological change and pollutant loads in determining floodplain lake ecosystem state.

Functional attributes of epilithic diatoms for palaeoenvironmental interpretations in South-West Greenland lakes.

Benthic diatoms are commonly used for palaeoenvironmental reconstruction in Arctic regions, but interpretation of their ecology remains challenging. We studied epilithic diatom assemblages from the shallow margins of 19 lakes from three areas (coast-inland-ice sheet margin) along a climate gradient in Kangerlussuaq, West Greenland during two periods; shortly after ice-off (spring) and in the middle of the growth season (summer). We aimed to understand the distribution of Arctic epilithic diatoms in relation to water chemistry gradients during the two seasons, to investigate their incorporation into lake sediments and to assess their applicability as palaeoenvironmental indicators. Diatoms were correlated with nutrients in the spring and alkalinity/major ions in the summer, when nutrients were depleted; approximately half of the variance explained was independent of spatial factors. When categorised by functional attributes, diatom seasonal succession differed among regions with the most obvious changes in inland lakes where summer temperatures are warmer, organic nutrient processing is prevalent and silicate is limiting. These conditions led to small, motile and adnate diatoms being abundant in inland lakes during the summer (Nitzschia spp., Encyonopsis microcephala), as these functional attributes are suited to living within complex mats of non-siliceous microbial biofilms. Seasonal succession in silica-rich lakes at the coast was less pronounced and assemblages included Tabellaria flocculosa (indicating more acidic conditions) and Hannaea arcus (indicating input from inflowing rivers). The nitrogen-fixing diatom Epithemia sorex increased from the coast to the ice sheet, negatively correlating with a gradient of reactive nitrogen. The presence of this diatom in Holocene sediment records alongside cyanobacterial carotenoids during arid periods of low nitrogen delivery, suggests that it is a useful indicator of nitrogen limitation. Nitzschia species appear to be associated with high concentrations of organic carbon and heterotrophy, but their poor representation in West Greenland lake sediments due to taphonomic processes limits their palaeoenvironmental application in this region. Proportions of epilithic taxa in lake sediment records of coastal lakes increased during some wetter periods of the Holocene, suggesting that snowpack-derived nutrient delivery may offer diatom taxa living at lake margins a competitive advantage over planktonic diatoms during the "moating" ice melt period. Thus, further research investigating linkages between epilithic diatoms, snowpack and nutrient delivery in seasonally frozen lakes is recommended as these taxa live on the 'front-line' during the spring and may be especially sensitive to changes in snowmelt conditions.

The Arctic in the Twenty-First Century: Changing Biogeochemical Linkages across a Paraglacial Landscape of Greenland.

The Kangerlussuaq area of southwest Greenland encompasses diverse ecological, geomorphic, and climate gradients that function over a range of spatial and temporal scales. Ecosystems range from the microbial communities on the ice sheet and moisture-stressed terrestrial vegetation (and their associated herbivores) to freshwater and oligosaline lakes. These ecosystems are linked by a dynamic glacio-fluvial-aeolian geomorphic system that transports water, geological material, organic carbon and nutrients from the glacier surface to adjacent terrestrial and aquatic systems. This paraglacial system is now subject to substantial change because of rapid regional warming since 2000. Here, we describe changes in the eco- and geomorphic systems at a range of timescales and explore rapid future change in the links that integrate these systems. We highlight the importance of cross-system subsidies at the landscape scale and, importantly, how these might change in the near future as the Arctic is expected to continue to warm.

Factors driving changes in freshwater mussel (Bivalvia, Unionida) diversity and distribution in Peninsular Malaysia.

Freshwater mussels (Bivalvia, Unionida) fulfil important ecosystem functions and are one of the most threatened freshwater taxa globally. Knowledge of freshwater mussel diversity, distribution and ecology in Peninsular Malaysia is extremely poor, and the conservation status of half of the species presumed to occur in the region has yet to be assessed. We conducted the first comprehensive assessment of Peninsular Malaysia's freshwater mussels based on species presence/absence and environmental data collected from 155 sites spanning all major river catchments and diverse habitat types. Through an integrative morphological-molecular approach we recognised nine native and one widespread non-native species, i.e. Sinanodonta woodiana. Two species, i.e. Pilsbryoconcha compressa and Pseudodon cambodjensis, had not been previously recorded from Malaysia, which is likely a result of morphological misidentifications of historical records. Due to their restriction to single river catchments and declining distributions, Hyriopsis bialata, possibly endemic to Peninsular Malaysia, Ensidens ingallsianus, possibly already extinct in the peninsula, and Rectidens sumatrensis, particularly require conservation attention. Equally, the Pahang, the Perak and the north-western river catchments are of particular conservation value due to the presence of a globally unique freshwater mussel fauna. Statistical relationships of 15 water quality parameters and mussel presence/absence identified acidification and nutrient pollution (eutrophication) as the most important anthropogenic factors threatening freshwater mussel diversity in Peninsular Malaysia. These factors can be linked to atmospheric pollution, deforestation, oil-palm plantations and a lack of functioning waste water treatment, and could be mitigated by establishing riparian buffers and improving waste water treatment for rivers running through agricultural and residential land.

Impacts of forestry planting on primary production in upland lakes from north-west Ireland.

Planted forests are increasing in many upland regions worldwide, but knowledge about their potential effects on algal communities of catchment lakes is relatively unknown. Here, the effects of afforestation were investigated using palaeolimnology at six upland lake sites in the north-west of Ireland subject to different extents of forest plantation cover (4-64% of catchment area). (210)Pb-dated sediment cores were analysed for carotenoid pigments from algae, stable isotopes of bulk carbon (δ(13)C) and nitrogen (δ(15)N), and C/N ratios. In lakes with >50% of their catchment area covered by plantations, there were two- to sixfold increases in pigments from cryptophytes (alloxanthin) and significant but lower increases (39-116%) in those from colonial cyanobacteria (canthaxanthin), but no response from biomarkers of total algal abundance (ß-carotene). In contrast, lakes in catchments with <20% afforestation exhibited no consistent response to forestry practices, although all lakes exhibited fluctuations in pigments and geochemical variables due to peat cutting and upland grazing prior to forest plantation. Taken together, patterns suggest that increases in cyanobacteria and cryptophyte abundance reflect a combination of mineral and nutrient enrichment associated with forest fertilization and organic matter influx which may have facilitated growth of mixotrophic taxa. This study demonstrates that planted forests can alter the abundance and community structure of algae in upland humic lakes of Ireland and Northern Ireland, despite long histories of prior catchment disturbance.

Acceleration of cyanobacterial dominance in north temperate-subarctic lakes during the Anthropocene.

Increases in atmospheric temperature and nutrients from land are thought to be promoting the expansion of harmful cyanobacteria in lakes worldwide, yet to date there has been no quantitative synthesis of long-term trends. To test whether cyanobacteria have increased in abundance over the past ~ 200 years and evaluate the relative influence of potential causal mechanisms, we synthesised 108 highly resolved sedimentary time series and 18 decadal-scale monitoring records from north temperate-subarctic lakes. We demonstrate that: (1) cyanobacteria have increased significantly since c. 1800 ce, (2) they have increased disproportionately relative to other phytoplankton, and (3) cyanobacteria increased more rapidly post c. 1945 ce. Variation among lakes in the rates of increase was explained best by nutrient concentration (phosphorus and nitrogen), and temperature was of secondary importance. Although cyanobacterial biomass has declined in some managed lakes with reduced nutrient influx, the larger spatio-temporal scale of sedimentary records show continued increases in cyanobacteria throughout the north temperate-subarctic regions.

Catchment-mediated atmospheric nitrogen deposition drives ecological change in two alpine lakes in SE Tibet.

The south-east margin of Tibet is highly sensitive to global environmental change pressures, in particular, high contemporary reactive nitrogen (Nr) deposition rates (ca. 40 kg ha(-1)  yr(-1) ), but the extent and timescale of recent ecological change is not well prescribed. Multiproxy analyses (diatoms, pigments and geochemistry) of (210) Pb-dated sediment cores from two alpine lakes in Sichuan were used to assess whether they have undergone ecological change comparable to those in Europe and North America over the last two centuries. The study lakes have contrasting catchment-to-lake ratios and vegetation cover: Shade Co has a relatively larger catchment and denser alpine shrub than Moon Lake. Both lakes exhibited unambiguous increasing production since the late 19th to early 20th. Principle component analysis was used to summarize the trends of diatom and pigment data after the little ice age (LIA). There was strong linear change in biological proxies at both lakes, which were not consistent with regional temperature, suggesting that climate is not the primary driver of ecological change. The multiproxy analysis indicated an indirect ecological response to Nr deposition at Shade Co mediated through catchment processes since ca. 1930, while ecological change at Moon Lake started earlier (ca. 1880) and was more directly related to Nr deposition (depleted δ(15) N). The only pronounced climate effect was evidenced by changes during the LIA when photoautotrophic groups shifted dramatically at Shade Co (a 4-fold increase in lutein concentration) and planktonic diatom abundance declined at both sites because of longer ice cover. The substantial increases in aquatic production over the last ca. 100 years required a substantial nutrient subsidy and the geochemical data point to a major role for Nr deposition although dust cannot be excluded. The study also highlights the importance of lake and catchment morphology for determining the response of alpine lakes to recent global environmental forcing.