Loss of beta-catenin triggers oxidative stress and impairs hematopoietic regeneration

Accidental or deliberate ionizing radiation exposure can be fatal due to widespread hematopoietic destruction. However, little is known about either the course of injury or the molecular pathways that regulate the subsequent regenerative response. Here we show that the Wnt signaling pathway is critically important for regeneration after radiation-induced injury. Using Wnt reporter mice, we show that radiation triggers activation of Wnt signaling in hematopoietic stem and progenitor cells. β-Catenin-deficient mice, which lack the ability to activate canonical Wnt signaling, exhibited impaired hematopoietic stem cell regeneration and bone marrow recovery after radiation. We found that, as part of the mechanism, hematopoietic stem cells lacking β-catenin fail to suppress the generation of reactive oxygen species and cannot resolve DNA double-strand breaks after radiation. Consistent with the impaired response to radiation, β-catenin-deficient mice are also unable to recover effectively after chemotherapy. Collectively, these data indicate that regenerative responses to distinct hematopoietic injuries share a genetic dependence on β-catenin and raise the possibility that modulation of Wnt signaling may be a path to improving bone marrow recovery after damage

Liprin-α1 modulates cancer cell signaling by transmembrane protein CD82 in adhesive membrane domains linked to cytoskeleton

BackgroundPPFIA1 is located at the 11q13 region commonly amplified in cancer. The protein liprin-α1 encoded by PPF1A1 contributes to the adhesive and invasive structures of cytoskeletal elements and is located at the invadosomes in cancer cells. However, the precise mechanism of liprin-α1 function in cancer progression has remained elusive.MethodsInvasion regulating activity of liprin-α1 was examined by analyzing the functions of squamous cell carcinoma of head and neck (HNSCC) cell lines in three-dimensional collagen I after RNAi mediated gene knockdown. Transcriptome profiling and Gene Set Enrichment Analysis from HNSCC and breast cancer cells were used to identify expression changes relevant to specific cellular localizations, biological processes and signaling pathways after PPFIA1knockdown. The significance of the results was assessed by relevant statistical methods (Wald and Benjamini-Hochberg). Localization of proteins associated to liprin-α1 was studied by immunofluorescence in 2D and 3D conditions. The association of PPFIA1 amplification to HNSCC patient survival was explored using The Cancer Genome Atlas data.ResultsIn this study, we show that liprin-α1 regulates biological processes related to membrane microdomains in breast carcinoma, as well as protein trafficking, cell-cell and cell-substrate contacts in HNSCC cell lines cultured in three-dimensional matrix. Importantly, we show that in all these cancer cells liprin-α1 knockdown leads to the upregulation of transmembrane protein CD82, which is a suppressor of metastasis in several solid tumors.ConclusionsOur results provide novel information regarding the function of liprin-α1 in biological processes essential in cancer progression. The results reveal liprin-α1 as a novel regulator of CD82, linking liprin-α1 to the cancer cell invasion and metastasis pathways.</div

Multitrophic biodiversity patterns and environmental descriptors of sub-Arctic lakes in northern Europe

Arctic and sub-Arctic lakes in northern Europe are increasingly threatened by climate change, which can affect their biodiversity directly by shifting thermal and hydrological regimes, and indirectly by altering landscape processes and catchment vegetation. Most previous studies of northern lake biodiversity responses to environmental changes have focused on only a single organismal group. Investigations at whole-lake scales that integrate different habitats and trophic levels are currently rare, but highly necessary for future lake monitoring and management. We analysed spatial biodiversity patterns of 74 sub-Arctic lakes in Norway, Sweden, Finland, and the Faroe Islands with monitoring data for at least three biological focal ecosystem components (FECs)—benthic diatoms, macrophytes, phytoplankton, littoral benthic macroinvertebrates, zooplankton, and fish—that covered both pelagic and benthic habitats and multiple trophic levels. We calculated the richnessrelative (i.e. taxon richness of a FEC in the lake divided by the total richness of that FEC in all 74 lakes) and the biodiversity metrics (i.e. taxon richness, inverse Simpson index (diversity), and taxon evenness) of individual FECs using presence–absence and abundance data, respectively. We then investigated whether the FEC richnessrelative and biodiversity metrics were correlated with lake abiotic and geospatial variables. We hypothesised that (1) individual FECs would be more diverse in a warmer and wetter climate (e.g. at lower latitudes and/or elevations), and in hydrobasins with greater forest cover that could enhance the supply of terrestrial organic matter and nutrients that stimulated lake productivity; and (2) patterns in FEC responses would be coupled among trophic levels. Results from redundancy analyses showed that the richnessrelative of phytoplankton, macrophytes, and fish decreased, but those of the intermediate trophic levels (i.e. macroinvertebrates and zooplankton) increased with decreasing latitude and/or elevation. Fish richnessrelative and diversity increased with increasing temporal variation in climate (temperature and/or precipitation), ambient nutrient concentrations (e.g. total nitrogen) in lakes, and woody vegetation (e.g. taiga forest) cover in hydrobasins, whereas taxon richness of macroinvertebrates and zooplankton decreased with increasing temporal variation in climate. The similar patterns detected for richnessrelative of fish, macrophytes, and phytoplankton could be caused by similar responses to the environmental descriptors, and/or the beneficial effects of macrophytes as habitat structure. By creating habitat, macrophytes may increase fish diversity and production, which in turn may promote higher densities and probably more diverse assemblages of phytoplankton through trophic cascades. Lakes with greater fish richnessrelative tended to have greater average richnessrelative among FECs, suggesting that fish are a potential indicator for overall lake biodiversity. Overall, the biodiversity patterns observed along the environmental gradients were trophic-level specific, indicating that an integrated food-web perspective may lead to a more holistic understanding of ecosystem biodiversity in future monitoring and management of high-latitude lakes. In future, monitoring should also focus on collecting more abundance data for fish and lower trophic levels in both benthic and pelagic habitats. This may require more concentrated sampling effort on fewer lakes at smaller spatial scales, while continuing to sample lakes distributed along environmental gradients.Peer reviewe

First circumpolar assessment of Arctic freshwater phytoplankton and zooplankton diversity : Spatial patterns and environmental factors

Arctic freshwaters are facing multiple environmental pressures, including rapid climate change and increasing land-use activities. Freshwater plankton assemblages are expected to reflect the effects of these stressors through shifts in species distributions and changes to biodiversity. These changes may occur rapidly due to the short generation times and high dispersal capabilities of both phyto- and zooplankton. Spatial patterns and contemporary trends in plankton diversity throughout the circumpolar region were assessed using data from more than 300 lakes in the U.S.A. (Alaska), Canada, Greenland, Iceland, the Faroe Islands, Norway, Sweden, Finland, and Russia. The main objectives of this study were: (1) to assess spatial patterns of plankton diversity focusing on pelagic communities; (2) to assess dominant component of beta diversity (turnover or nestedness); (3) to identify which environmental factors best explain diversity; and (4) to provide recommendations for future monitoring and assessment of freshwater plankton communities across the Arctic region. Phytoplankton and crustacean zooplankton diversity varied substantially across the Arctic and was positively related to summer air temperature. However, for zooplankton, the positive correlation between summer temperature and species numbers decreased with increasing latitude. Taxonomic richness was lower in the high Arctic compared to the sub- and low Arctic for zooplankton but this pattern was less clear for phytoplankton. Fennoscandia and inland regions of Russia represented hotspots for, respectively, phytoplankton and zooplankton diversity, whereas isolated regions had lower taxonomic richness. Ecoregions with high alpha diversity generally also had high beta diversity, and turnover was the most important component of beta diversity in all ecoregions. For both phytoplankton and zooplankton, climatic variables were the most important environmental factors influencing diversity patterns, consistent with previous studies that examined shorter temperature gradients. However, barriers to dispersal may have also played a role in limiting diversity on islands. A better understanding of how diversity patterns are determined by colonisation history, environmental variables, and biotic interactions requires more monitoring data with locations dispersed evenly across the circumpolar Arctic. Furthermore, the importance of turnover in regional diversity patterns indicates that more extensive sampling is required to fully characterise the species pool of Arctic lakes.Peer reviewe

Biodiversity patterns of Arctic diatom assemblages in lakes and streams: Current reference conditions and historical context for biomonitoring

Comprehensive assessments of contemporary diatom distributions across the Arctic remain scarce. Furthermore, studies tracking species compositional differences across space and time, as well as diatom responses to climate warming, are mainly limited to paleolimnological studies due to a lack of routine monitoring in lakes and streams across vast areas of the Arctic. The study aims to provide a spatial assessment of contemporary species distributions across the circum-Arctic, establish contemporary biodiversity patterns of diatom assemblages to use as reference conditions for future biomonitoring assessments, and determine pre-industrial baseline conditions to provide historical context for modern diatom distributions. Diatom assemblages were assessed using information from ongoing regulatory monitoring programmes, individual research projects, and from surface sediment layers obtained from lake cores. Pre-industrial baseline conditions as well as the nature, direction and magnitude of changes in diatom assemblages over the pastc.200 years were determined by comparing surface sediment samples (i.e. containing modern assemblages) with a sediment interval deposited prior to the onset of significant anthropogenic activities (i.e. containing pre-1850 assemblages), together with an examination of diatoms preserved in contiguous samples from dated sediment cores. We identified several biotypes with distinct diatom assemblages using contemporary diatom data from both lakes and streams, including a biotype typical for High Arctic regions. Differences in diatom assemblage composition across circum-Arctic regions were gradual rather than abrupt. Species richness was lowest in High Arctic regions compared to Low Arctic and sub-Arctic regions, and higher in lakes than in streams. Dominant diatom taxa were not endemic to the Arctic. Species richness in both lakes and streams reached maximum values between 60 degrees N and 75 degrees N but was highly variable, probably reflecting differences in local and regional environmental factors and possibly sampling effort. We found clear taxon-specific differences between contemporary and pre-industrial samples that were often specific to both ecozone and lake depth. Regional patterns of species turnover (beta-diversity) in the pastc.200 years revealed that regions of the Canadian High Arctic and the Hudson Bay Lowlands to the south showed most compositional change, whereas the easternmost regions of the Canadian Arctic changed least. As shown in previous Arctic diatom studies, global warming has already affected these remote high latitude ecosystems. Our results provide reference conditions for future environmental monitoring programmes in the Arctic. Furthermore, diatom taxa identification and harmonisation require improvement, starting with circum-Arctic intercalibrations. Despite the challenges posed by the remoteness of the Arctic, our study shows the need for routine monitoring programmes that have a wide geographical coverage for both streams and lakes

Circumpolar patterns of Arctic freshwater fish biodiversity : A baseline for monitoring

1. Climate change, biological invasions, and anthropogenic disturbance pose a threat to the biodiversity and function of Arctic freshwater ecosystems. Understanding potential changes in fish species distribution and richness is necessary, given the great importance of fish to the function of freshwater ecosystems and as a resource to humans. However, information gaps limit large-scale studies and our ability to determine patterns and trends in space and time. This study takes the first step in determining circumpolar patterns of fish species richness and composition, which provides a baseline to improve both monitoring and conservation of Arctic freshwater biodiversity. 2. Information on species presence/absence was gathered from the Circumpolar Biodiversity Monitoring Program's Freshwater Database and used to examine patterns of freshwater fish γ-, α-, and β-diversity across 234° of longitude in the Arctic. The metrics of diversity provided information on species richness and composition across hydrobasins, ecoregions, and Arctic zones. 3. Circumpolar patterns of fish species biodiversity varied with latitude, isolation, and coarse ecoregion characteristics; patterns were consistent with historic and contemporary barriers to colonisation and environmental characteristics. Gamma-diversity was lower in the high Arctic compared to lower latitude zones, but α-diversity did not decrease with increasing latitude below 71°N, reflecting glacial history. Alpha-diversity was reduced to a single species, Arctic charr Salvelinus alpinus, in ecoregions above 71°N, where γ-diversity was the lowest. Beta-diversity indicated little variation in the composition and richness of species across the High Arctic; at lower latitudes, ecoregions contained more species, although species composition turned over across large spatial extents. 4. In an analysis of five ecoregions in the circumpolar Arctic, physical isolation, and ecoregion area and topography were identified as strong drivers of γ-, α-, and β-diversity. Physical isolation reduced the γ- and α-diversity, and changes in β-diversity between adjacent locations were due mainly to losses in species richness, rather than due to differences in species composition. Heterogeneity of habitats, environmental gradients, and geographic distance probably contributed to patterns of fish dissimilarity within and across ecoregions. 5. This study presents the first analysis of large-scale patterns of freshwater fish biodiversity in the circumpolar Arctic. However, information gaps in space, time, and among taxonomic groups remain. Future inclusion of extensive archive and new data will allow future studies to test for changes and drivers of the observed patterns of biodiversity. This is important given the potential impacts of ongoing and accelerating climate change, land use, and biotic exchange on Arctic fish biodiversity