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Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation 1 , 2 . Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation 3 , we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt’s lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis. Proferroptotic activity of 7-dehydrocholesterol reductase is shown along with an unexpected prosurvival function of its substrate, 7-dehydrocholesterol, indicating a cell-intrinsic mechanism that could be used by cancer cells to protect phospholipids from oxidative damage and escape ferroptosis.

BackgroundUrban streams are characterised by species-poor and frequently disturbed communities. The recovery of heavily polluted urban streams is challenging but the simple community structure makes recolonisation patterns more transparent. Therefore, they are generally applicable model systems for recolonisation of restored streams. Principal questions of stream restoration concern the drivers and patterns of recolonisation processes. Rarely, recolonisation of restored streams is recorded for a sufficient time to observe patterns of habitat and community development in detail. Over 10 years, we monitored benthic habitat changes and macroinvertebrate communities of eight restored sites in an urban stream network that was formerly used as an open sewer and thus, almost uninhabitable for macroinvertebrates prior to restoration. We analysed changes in environmental variables and communities with a selection of multi-variate analyses and identified indicator species in successional stages.ResultsProportions of stony substrate and conductivity decreased over time since restoration, while the riparian vegetation cover increased along with the amount of sandy substrate. The communities fluctuated strongly after restoration but began to stabilise after around eight years. TITAN analysis identified 9 species, (e.g. the mayfly Cloeon dipterum and the beetle Agabus didymus), whose abundances decreased with time since restoration, and 19 species with an increasing abundance trend (e.g. several Trichopteran species, which colonised once specific habitats developed). Woody riparian vegetation cover and related variables were identified as major driver for changes in species abundance. In the last phase of the observation period, a dry episode resulted in complete dewatering of some sites. These temporarily dried sections were recolonised much more rapidly compared to the recolonisation following restoration.ConclusionsOur results underline that community changes following urban stream restoration are closely linked to the evolving environmental conditions of restored streams, in particular habitat availability initialised by riparian vegetation. It takes about a decade for the development of a rich and stable community. Even in streams that were almost completely lacking benthic invertebrates before restoration, the establishment of a diverse macroinvertebrate community is possible, underlining the potential for habitat restoration in formerly heavily polluted urban areas.

Background Understanding the temporal development of community assembly processes is essential for assessing the recovery of degraded ecosystems after restoration. Community development in restored streams is often slow or absent, due to inadequate restoration, catchment-scale pressures, and/or colonisation barriers. Recovery processes involve three key filters: dispersal, environmental conditions and biotic interactions. Dispersal is critical for initial colonisation, while environmental conditions influence successful population establishment. Lastly, as available niches fill, biotic interactions, such as competition, gain importance. Despite the presence of many theories on how these three filters interact during community assembly, they have rarely been investigated simultaneously. Our detailed species- and site-specific approach allowed us to analyse the three filters in a hierarchical analysis. We assessed the effect of the three filters, by examining benthic invertebrate communities at 20 sites in the Boye catchment (Western Germany). The Boye and most of its tributaries were used as open sewers for a century, i.e. they were concrete channels transporting untreated sewage before gradual restoration was started in the 1990s. The bank reinforcements and concrete beds were removed, while riparian vegetation was left to natural succession. Accordingly, the sites were grouped as 'unimpacted', 'recently restored' (< 4 years), and 'mature restored' (> 10 years). An additional 28 sites provided information on distances to source populations, while the species’ habitat suitability assessed environmental filtering. Biotic (interaction) filtering was evaluated through trait overlap analysis. Results Communities at recently restored sites differed from mature and unimpacted sites, while mature sites resembled unimpacted ones. Taxa at recently restored sites had nearer source populations, while those at mature and unimpacted sites better matched present habitats. Trait overlap did not differ between present and absent taxa. Conclusions Our results indicate that dispersal was essential in early recovery stages, with mass effects from upstream sources supporting taxa found at recently restored sites despite low habitat suitability. Over time, habitat suitability became more influential, shaping mature communities. Competition appeared relatively unimportant, yet competitive exclusion may explain small proportions of absent taxa at mature and recently restored sites. Hence, to effectively support stream recovery, it is essential to consider how different filtering processes operate at various stages of the recovery process. For example, mature communities could further develop if habitat availability increases, while the connectivity to source populations would only play a minor role.

The present study provides new insight into suitable microsporidian–host associations. It relates regional and continental-wide host specialization in microsporidians infecting amphipods to degraded and recovering habitats across 2 German river catchments. It provides a unique opportunity to infer the persistence of parasites following anthropogenic disturbance and their establishment in restored rivers. Amphipods were collected in 31 sampling sites with differing degradation and restoration gradients. Specimens were morphologically (hosts) and molecularly identified (host and parasites). Amphipod diversity and abundance, microsporidian diversity, host phylogenetic specificity and continental-wide β-specificity were investigated and related to each other and/or environmental variables. Fourteen microsporidian molecular operational taxonomic units (MOTUs), mainly generalist parasites, infecting 6 amphipod MOTUs were detected, expanding the current knowledge on the host range by 17 interactions. There was no difference in microsporidian diversity and host specificity among restored and near-natural streams (Boye) or between those located in urban and rural areas (Kinzig). Similarly, microsporidian diversity was generally not influenced by water parameters. In the Boye catchment, host densities did not influence microsporidian MOTU richness across restored and near-natural sites. High host turnover across the geographical range suggests that neither environmental conditions nor host diversity plays a significant role in the establishment into restored areas. Host diversity and environmental parameters do not indicate the persistence and dispersal of phylogenetic host generalist microsporidians in environments that experienced anthropogenic disturbance. Instead, these might depend on more complex mechanisms such as the production of resistant spores, host switching and host dispersal acting individually or conjointly.

Background The global freshwater biodiversity crisis has led to widespread implementation of measures to counteract environmental degradation and biodiversity loss. While these efforts aim to foster recovery, intensifying stressors continue to drive complex biotic responses, the trajectories and drivers of which are insufficiently understood. This study examines the roles of abiotic stressors, biotic interactions (e.g., competition), and land use in shaping ecological status changes across Germany, using data from 1599 river sites sampled at least twice between 2004 and 2022. Results Changes in abiotic stressors emerged as the most consistent drivers of ecological status, explaining substantial variation ( R 2  = 0.39) and similar slopes for recovery ( β  = − 0.11) and degradation ( β  = − 0.10). Biotic interactions, particularly interspecific competition, also influenced the ecological status ( R 2  = 0.11), with stronger positive effects observed during recovery ( β  = 2.99) compared to degradation ( β  = 1.59). Land use effects varied by context: Streams in catchments with higher cropland or urban areas showed greater likelihood of recovery, whereas streams in forested catchments were more prone to degradation. These results highlight the interplay of abiotic and biotic factors in driving ecological processes of recovery and degradation. Conclusion These findings emphasize the critical role of improving water quality for enhancing biodiversity and ecological status in rivers, while also demonstrating the importance of biotic interactions and land use context in driving recovery dynamics. Integrating these insights into management and restoration efforts can enhance freshwater ecosystem resilience in the face of escalating environmental pressures.

Abstract Aims Volume overload (VO) and pressure overload (PO) induce differential cardiac remodelling responses including distinct signalling pathways. Extracellular signal-regulated kinases 1 and 2 (ERK1/2), key signalling components in the mitogen-activated protein kinase (MAPK) pathways, modulate cardiac remodelling during pressure overload (PO). This study aimed to assess their role in VO-induced cardiac remodelling as this was unknown. Methods and results Aortocaval fistula (Shunt) surgery was performed in mice to induce cardiac VO. Two weeks of Shunt caused a significant reduction of cardiac ERK1/2 activation in wild type (WT) mice as indicated by decreased phosphorylation of the TEY (Thr-Glu-Tyr) motif (−28% as compared with Sham controls, P < 0.05). Phosphorylation of other MAPKs was unaffected. For further assessment, transgenic mice with cardiomyocyte-specific ERK2 overexpression (ERK2tg) were studied. At baseline, cardiac ERK1/2 phosphorylation in ERK2tg mice remained unchanged compared with WT littermates, and no overt cardiac phenotype was observed; however, cardiac expression of the atrial natriuretic peptide was increased on messenger RNA (3.6-fold, P < 0.05) and protein level (3.1-fold, P < 0.05). Following Shunt, left ventricular dilation and hypertrophy were similar in ERK2tg mice and WT littermates. Left ventricular function was maintained, and changes in gene expression indicated reactivation of the foetal gene program in both genotypes. No differences in cardiac fibrosis and kinase activation was found amongst all experimental groups, whereas apoptosis was similarly increased through Shunt in ERK2tg and WT mice. Conclusions VO-induced eccentric hypertrophy is associated with reduced cardiac ERK1/2 activation in vivo. Cardiomyocyte-specific overexpression of ERK2, however, does not alter cardiac remodelling during VO. Future studies need to define the pathophysiological relevance of decreased ERK1/2 signalling during VO.

Community development in restored streams is often slow or even absent, but reasons remain obscure. Inadequate restoration measures, catchment-scale pressures, community closure and colonization barriers all may prevent or slow down recovery processes. For initial colonization, dispersal processes are supposed to be most important, which are referred to as dispersal filter. Environmental conditions of a restored reach determine if a dispersing species can successfully establish (environmental filter). Lastly, while available niches at those reaches fill up, biotic interactions, such as competition, become more important (biotic filter). To investigate the importance of these different filters, we compared benthic invertebrate communities of 20 sites in the Boye catchment (Western Germany), a former open sewer system. The sites were grouped, based on the years since restoration, into ‘unimpacted’ (never restored), ‘recently restored’ (< 4 years) and ‘mature restored’ (> 10 years) sites. Data collected at 28 additional sites in the catchment informed us on distances to potential source populations. Habitat suitability describes the fit between environmental conditions (abiotic site data) and species preferences and was used to assess the role of environmental filtering. We evaluated the role of the biotic filter based on trait overlap, referring to possible interspecific competition. Communities collected at recently restored sites differed from those of mature restored and unimpacted sites. Taxa present at recently restored and mature sites had closer source populations than those of unimpacted sites. Taxa at mature and unimpacted sites had a better fit to the present habitats than those of recently restored sites. The trait overlap did not differ between co-occurring and not co-occurring taxa at any of the site groups. Our findings show that communities of mature restored sites that have been restored more than 10 years ago, resembled those of unimpacted sites. Dispersal was most important in early years of recovery. Taxa occurrences at sites with nearby source populations and low habitat suitability are likely the result of high rates of dispersal from upstream sources (mass effects). These can be caused by hatching events or environmental disturbances. Habitat suitability played a larger role for communities at mature and unimpacted sites which indicates that optimal communities shape over time. We did not find indications that competition played a role for community assembly. Hence, dispersal and habitat suitability were most relevant for species’ occurrences. Competition could be more important on micro scales and the results may differ if species abundances are taken into account.