The GEF Trio controls endothelial cell size and arterial remodeling downstream of Vegf signaling in both zebrafish and cell models

Arterial networks enlarge in response to increase in tissue metabolism to facilitate flow and nutrient delivery. Typically, the transition of a growing artery with a small diameter into a large caliber artery with a sizeable diameter occurs upon the blood flow driven change in number and shape of endothelial cells lining the arterial lumen. Here, using zebrafish embryos and endothelial cell models, we describe an alternative, flow independent model, involving enlargement of arterial endothelial cells, which results in the formation of large diameter arteries. Endothelial enlargement requires the GEF1 domain of the guanine nucleotide exchange factor Trio and activation of Rho-GTPases Rac1 and RhoG in the cell periphery, inducing F-actin cytoskeleton remodeling, myosin based tension at junction regions and focal adhesions. Activation of Trio in developing arteries in vivo involves precise titration of the Vegf signaling strength in the arterial wall, which is controlled by the soluble Vegf receptor Flt1. Arterial flow regulates artery diameter but other mechanisms may also affect this. Here, the authors show that the guanine nucleotide exchange factor Trio and GTPases Rac1 and RhoG, triggers F-actin remodeling in arterial endothelial cells, independent of flow, to enhance lumen diameter in zebrafish and cell models.Peer reviewe

Effects of ocean sprawl on ecological connectivity: impacts and solutions

The growing number of artificial structures in estuarine, coastal and marine environments is causing “ocean sprawl”. Artificial structures do not only modify marine and coastal ecosystems at the sites of their placement, but may also produce larger-scale impacts through their alteration of ecological connectivity - the movement of organisms, materials and energy between habitat units within seascapes. Despite the growing awareness of the capacity of ocean sprawl to influence ecological connectivity, we lack a comprehensive understanding of how artificial structures modify ecological connectivity in near- and off-shore environments, and when and where their effects on connectivity are greatest. We review the mechanisms by which ocean sprawl may modify ecological connectivity, including trophic connectivity associated with the flow of nutrients and resources. We also review demonstrated, inferred and likely ecological impacts of such changes to connectivity, at scales from genes to ecosystems, and potential strategies of management for mitigating these effects. Ocean sprawl may alter connectivity by: (1) creating barriers to the movement of some organisms and resources - by adding physical barriers or by modifying and fragmenting habitats; (2) introducing new structural material that acts as a conduit for the movement of other organisms or resources across the landscape; and (3) altering trophic connectivity. Changes to connectivity may, in turn, influence the genetic structure and size of populations, the distribution of species, and community structure and ecological functioning. Two main approaches to the assessment of ecological connectivity have been taken: (1) measurement of structural connectivity - the configuration of the landscape and habitat patches and their dynamics; and (2) measurement of functional connectivity - the response of organisms or particles to the landscape. Our review reveals the paucity of studies directly addressing the effects of artificial structures on ecological connectivity in the marine environment, particularly at large spatial and temporal scales. With the ongoing development of estuarine and marine environments, there is a pressing need for additional studies that quantify the effects of ocean sprawl on ecological connectivity. Understanding the mechanisms by which structures modify connectivity is essential if marine spatial planning and eco-engineering are to be effectively utilised to minimise impacts

Contrasting lake ice responses to winter climate indicate future variability and trends on the Alaskan Arctic Coastal Plain

© 2018 The Author(s). Published by IOP Publishing Ltd. Strong winter warming has dominated recent patterns of climate change along the Arctic Coastal Plain (ACP) of northern Alaska. The full impact of arctic winters may be best manifest by freshwater ice growth and the extent to which abundant shallow ACP lakes freeze solid with bedfast ice by the end of winter. For example, winter conditions of 2016-17 produced record low extents of bedfast ice across the ACP. In addition to high air temperatures, the causes varied from deep snow accumulation on the Barrow Peninsula to high late season rainfall and lake levels farther east on the ACP. In contrast, the previous winter of 2015-16 was also warm, but low snowpack and high winds caused relatively thick lake ice to develop and corresponding high extents of bedfast ice on the ACP. This recent comparison of extreme variation in lake ice responses between two adjacent regions and years in the context of long-term climate and ice records highlights the complexity associated with weather conditions and climate change in the Arctic. Recent observations of maximum ice thickness (MIT) compared to simulated MIT from Weather Research and Forcing (Polar-WRF) model output show greater departure toward thinner ice than predicted by models, underscoring this uncertainty and the need for sustained observations. Lake ice thickness and the extent of bedfast ice not only indicate the impact of arctic winters, but also directly affect sublake permafrost, winter water supply for industry, and overwinter habitat availability. Therefore, tracking freshwater ice responses provides a comprehensive picture of winter, as well as summer, weather conditions and climate change with implications to broader landscape, ecosystem, and resource responses in the Arctic

Towards panarctic mapping of drained lake basins in permafrost regions

Lakes and drained lake basins (DLBs) are dominant landforms across Arctic lowland regions. The long-term dynamics of lake formation and drainage is evident in the abundance of lakes and DLBs covering as much as 80% of the landscape in various regions of Arctic Alaska, Russia, and Canada. Lake drainage can be triggered through different mechanisms such as lake tapping by an adjacent stream, bank overflow or ice wedge degradation. Following drainage, DLBs can become valuable grazing land for caribou and reindeer as well as usable land for infrastructure development due to low ground ice content in recent DLBs. In addition, DLBs can be sites for soil organic carbon accumulation in the form of peat which also play a role for carbon cycling. Comprehensive and accurate mapping of DLB distribution, age and drainage mechanism, will further inform our understanding of their role in permafrost landscape evolution across varying timescales. DLBs differ from the surrounding terrain in vegetation structure and composition, soil moisture, elevation, size and types of ice-wedge polygons and other parameters that make them an identifiable target based on remote sensing data. Here, we present a novel approach to map DLBs in permafrost landscapes with a specific focus on the North Slope of Alaska as well as select areas in Siberia and northwestern Canada. To map DLBs, we combined multispectral satellite imagery (Landsat-8 and Sentinel-2), Synthetic Aperture Radar (SAR) acquisitions (Sentinel-1), and DEM data (ArcticDEM). To cover the entire study area in each region, we included Landsat-8 acquisitions from all available years and Sentinel-2 for 2016 and 2018 to create cloud-free mosaics. The classification combines methodologies from pixel-based and object-based image analysis. To allow for processing of these large datasets that cover more than 200.000 km2, a classification workflow was developed in Google Earth Engine. Preliminary results show good agreement of our classification with previously published data sets for subsets of our North Slope study area. This work marks the first attempt to map DLBs at the pan-Arctic scale. Our results highlight the importance of treating areas of different surficial geology and vegetation communities separately in the classification process to ensure higher classification accuracy

Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers

Aberrations in genes coding for subunits of the BRG1/BRM associated factor (BAF) chromatin remodeling complexes are highly abundant in human cancers. Currently, it is not understood how these mostly loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer-type-specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knockout cell lines deficient for 22 BAF subunits. We observe strong, specific and sometimes discordant alterations dependent on the targeted subunit and show that these explain intracomplex codependencies, including the synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest approaches to therapeutically target BAF-mutant cancers