Permafrost microbial communities and functional genes are structured by latitudinal and soil geochemical gradients.

Permafrost underlies approximately one quarter of Northern Hemisphere terrestrial surfaces and contains 25-50% of the global soil carbon (C) pool. Permafrost soils and the C stocks within are vulnerable to ongoing and future projected climate warming. The biogeography of microbial communities inhabiting permafrost has not been examined beyond a small number of sites focused on local-scale variation. Permafrost is different from other soils. Perennially frozen conditions in permafrost dictate that microbial communities do not turn over quickly, thus possibly providing strong linkages to past environments. Thus, the factors structuring the composition and function of microbial communities may differ from patterns observed in other terrestrial environments. Here, we analyzed 133 permafrost metagenomes from North America, Europe, and Asia. Permafrost biodiversity and taxonomic distribution varied in relation to pH, latitude and soil depth. The distribution of genes differed by latitude, soil depth, age, and pH. Genes that were the most highly variable across all sites were associated with energy metabolism and C-assimilation. Specifically, methanogenesis, fermentation, nitrate reduction, and replenishment of citric acid cycle intermediates. This suggests that adaptations to energy acquisition and substrate availability are among some of the strongest selective pressures shaping permafrost microbial communities. The spatial variation in metabolic potential has primed communities for specific biogeochemical processes as soils thaw due to climate change, which could cause regional- to global- scale variation in C and nitrogen processing and greenhouse gas emissions.

Photoswitchable Molecular Glues Enable Optical Control of Transcription Factor Degradation.

Immunomodulatory drugs (IMiDs), which include thalidomide and its derivatives, have emerged as the standard of care against multiple myeloma. They function as molecular glues that bind to the E3 ligase cereblon (CRBN) and induce protein interactions with neosubstrates, including the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). The subsequent ubiquitylation and degradation of these transcription factors underlies the antiproliferative activity of IMiDs. Here, we introduce photoswitchable immunomodulatory drugs (PHOIMiDs) that can be used to degrade Ikaros and Aiolos in a light-dependent fashion. Our lead compound shows minimal activity in the dark and becomes an active degrader upon irradiation with violet light. It shows high selectivity over other transcription factors, regardless of its state, and could therefore be used to control the levels of Ikaros and Aiolos with high spatiotemporal precision.

Optopharmacological tools for precise spatiotemporal control of oxytocin signaling in the central nervous system and periphery.

Oxytocin is a neuropeptide critical for maternal physiology and social behavior, and is thought to be dysregulated in several neuropsychiatric disorders. Despite the biological and neurocognitive importance of oxytocin signaling, methods are lacking to activate oxytocin receptors with high spatiotemporal precision in the brain and peripheral mammalian tissues. Here we developed and validated caged analogs of oxytocin which are functionally inert until cage release is triggered by ultraviolet light. We examined how focal versus global oxytocin application affected oxytocin-driven Ca2+ wave propagation in mouse mammary tissue. We also validated the application of caged oxytocin in the hippocampus and auditory cortex with electrophysiological recordings in vitro, and demonstrated that oxytocin uncaging can accelerate the onset of mouse maternal behavior in vivo. Together, these results demonstrate that optopharmacological control of caged peptides is a robust tool with spatiotemporal precision for modulating neuropeptide signaling throughout the brain and body.

Development of Light-Activated LXR Agonists.

Activation of the oxysterol-sensing transcription factor liver X receptor (LXR) has been studied as a therapeutic strategy in metabolic diseases and cancer but is compromised by the side effects of LXR agonists. Local LXR activation in cancer treatment may offer an opportunity to overcome this issue suggesting potential uses of photopharmacology. We report the computer-aided development of photoswitchable LXR agonists based on the T0901317 scaffold, which is a known LXR agonist. Azologization and structure-guided structure-activity relationship evaluation enabled the design of an LXR agonist, which activated LXR with low micromolar potency in its light-induced (Z)-state and was inactive as (E)-isomer. This tool sensitized human lung cancer cells to chemotherapeutic treatment in a light-dependent manner supporting potential of locally activated LXR agonists as adjuvant cancer treatment.

Identifying historical and future potential lake drainage events on the western Arctic coastal plain of Alaska.

Arctic lakes located in permafrost regions are susceptible to catastrophic drainage. In this study, we reconstructed historical lake drainage events on the western Arctic Coastal Plain of Alaska between 1955 and 2017 using USGS topographic maps, historical aerial photography (1955), and Landsat Imagery (ca. 1975, ca. 2000, and annually since 2000). We identified 98 lakes larger than 10 ha that partially (>25% of area) or completely drained during the 62-year period. Decadal-scale lake drainage rates progressively declined from 2.0 lakes/yr (1955-1975), to 1.6 lakes/yr (1975-2000), and to 1.2 lakes/yr (2000-2017) in the ~30,000-km2 study area. Detailed Landsat trend analysis between 2000 and 2017 identified two years, 2004 and 2006, with a cluster (five or more) of lake drainages probably associated with bank overtopping or headward erosion. To identify future potential lake drainages, we combined the historical lake drainage observations with a geospatial dataset describing lake elevation, hydrologic connectivity, and adjacent lake margin topographic gradients developed with a 5-m-resolution digital surface model. We identified ~1900 lakes likely to be prone to drainage in the future. Of the 20 lakes that drained in the most recent study period, 85% were identified in this future lake drainage potential dataset. Our assessment of historical lake drainage magnitude, mechanisms and pathways, and identification of potential future lake drainages provides insights into how arctic lowland landscapes may change and evolve in the coming decades to centuries.

Tundra be dammed: Beaver colonization of the Arctic.

Increasing air temperatures are changing the arctic tundra biome. Permafrost is thawing, snow duration is decreasing, shrub vegetation is proliferating, and boreal wildlife is encroaching. Here we present evidence of the recent range expansion of North American beaver (Castor canadensis) into the Arctic, and consider how this ecosystem engineer might reshape the landscape, biodiversity, and ecosystem processes. We developed a remote sensing approach that maps formation and disappearance of ponds associated with beaver activity. Since 1999, 56 new beaver pond complexes were identified, indicating that beavers are colonizing a predominantly tundra region (18,293 km2 ) of northwest Alaska. It is unclear how improved tundra stream habitat, population rebound following overtrapping for furs, or other factors are contributing to beaver range expansion. We discuss rates and likely routes of tundra beaver colonization, as well as effects on permafrost, stream ice regimes, and freshwater and riparian habitat. Beaver ponds and associated hydrologic changes are thawing permafrost. Pond formation increases winter water temperatures in the pond and downstream, likely creating new and more varied aquatic habitat, but specific biological implications are unknown. Beavers create dynamic wetlands and are agents of disturbance that may enhance ecosystem responses to warming in the Arctic.

Impact of Dose-Adjusted Melphalan in Obese Patients Undergoing Autologous Stem Cell Transplantation.

Limited guidance exists for dosing melphalan for autologous stem cell transplantation (ASCT) in the obese patient population, because the current literature reports conflicting clinical outcomes between obese and nonobese patients. In 2014, the American Society for Blood and Marrow Transplantation published conditioning chemotherapy dosing guidelines for obese patients and recommended dosing of melphalan using actual body weight (ABW) in the body surface area calculation. The practice at Barnes-Jewish Hospital has consistently been to dose melphalan using adjusted body weight (AdBW), with a 20% correction when a patient weighs ≥120% of his or her ideal body weight (IBW). The purpose of this study was to compare outcomes of melphalan ASCT in patients with multiple myeloma between obese (≥120% IBW) and nonobese (<120% IBW) populations. This retrospective, single-center study included adult patients with multiple myeloma undergoing first ASCT with melphalan conditioning between January 2009 and December 2012. Patient demographic data, transplantation characteristics, and clinical outcomes were collected. The primary outcome was 3-year event-free survival (EFS). Secondary outcomes included response at 100 days post-transplantation, 3-year overall survival, treatment-related mortality (TRM), time to neutrophil engraftment, and hospital length of stay (LOS). To ensure that melphalan dosage adjustment in the obese population did not impact efficacy, the primary outcome was assessed using a noninferiority design, with a predetermined noninferiority margin of 7%. Assuming a 70% 3-year EFS in the nonobese population, a noninferiority margin of 7%, a power of 80%, and an α value of .05, an analysis of 280 patients was required. A total of 270 patients, including 171 (63%) obese patients and 99 (37%) nonobese patients, met our inclusion criteria. Baseline characteristics were well matched between the 2 cohorts, including high-risk cytogenetics, disease severity at diagnosis, and use of maintenance therapy, with the only detectable differences related to weight itself. The 3-year EFS was 41% for the total cohort, with fewer events occurring in the obese cohort compared with the nonobese cohort (51% versus 40%; P = .0025). The 95% lower confidence limit established noninferiority. High-risk cytogenetics, disease severity at diagnosis, and therapy response pre- and post-ASCT were all associated with significantly shorter EFS. No between-group differences in TRM, time to engraftment, or hospital LOS were noted. This retrospective, single-center study found that using AdBW to dose melphalan in obese patients was not inferior to the nonobese population in terms of 3-year EFS. This study adds to the limited evidence on melphalan dosing and suggests that transplantation efficacy is not affected by AdBW dosing in obese patients. Further studies are needed to provide additional insight into the pharmacokinetic differences and best dosing practices for obese patients.

A lake-centric geospatial database to guide research and inform management decisions in an Arctic watershed in northern Alaska experiencing climate and land-use changes.

Lakes are dominant and diverse landscape features in the Arctic, but conventional land cover classification schemes typically map them as a single uniform class. Here, we present a detailed lake-centric geospatial database for an Arctic watershed in northern Alaska. We developed a GIS dataset consisting of 4362 lakes that provides information on lake morphometry, hydrologic connectivity, surface area dynamics, surrounding terrestrial ecotypes, and other important conditions describing Arctic lakes. Analyzing the geospatial database relative to fish and bird survey data shows relations to lake depth and hydrologic connectivity, which are being used to guide research and aid in the management of aquatic resources in the National Petroleum Reserve in Alaska. Further development of similar geospatial databases is needed to better understand and plan for the impacts of ongoing climate and land-use changes occurring across lake-rich landscapes in the Arctic.

Predicting Late Winter Dissolved Oxygen Levels in Arctic Lakes Using Morphology and Landscape Metrics.

Overwintering habitat for Arctic freshwater fish is essential, such that understanding the distribution of winter habitat quality at the landscape-scale is warranted. Adequate dissolved oxygen (DO) is a major factor limiting habitat quality in the Arctic region where ice cover can persist for 8 months each year. Here we use a mixed-effect model developed from 20 lakes across northern Alaska to assess which morphology and landscape attributes can be used to predict regional overwintering habitat quality. Across all lakes, we found that the majority of the variations in late winter DO can be explained by lake depth and littoral area. In shallow lakes (<4 m), we found evidence that additional variables such as elevation, lake area, ice cover duration, and snow depth were associated with DO regimes. Low DO regimes were most typical of shallow lakes with large littoral areas and lakes that had high DO regimes often were lakes with limited littoral areas and deeper water. Our analysis identifies metrics that relate to late winter DO regimes in Arctic lakes that can aid managers in understanding which lakes will likely provide optimum DO for overwintering habitat. Conversely, lakes which predicted to have marginal winter DO levels may be vulnerable to disturbances that could lower DO below critical thresholds to support sensitive fish. In regions where lakes are also used by humans for industrial winter water supply, such as ice-road construction for oil and gas development, these findings will be vital for the management of resources and protection of Arctic fish.

Recent Arctic tundra fire initiates widespread thermokarst development.

Fire-induced permafrost degradation is well documented in boreal forests, but the role of fires in initiating thermokarst development in Arctic tundra is less well understood. Here we show that Arctic tundra fires may induce widespread thaw subsidence of permafrost terrain in the first seven years following the disturbance. Quantitative analysis of airborne LiDAR data acquired two and seven years post-fire, detected permafrost thaw subsidence across 34% of the burned tundra area studied, compared to less than 1% in similar undisturbed, ice-rich tundra terrain units. The variability in thermokarst development appears to be influenced by the interaction of tundra fire burn severity and near-surface, ground-ice content. Subsidence was greatest in severely burned, ice-rich upland terrain (yedoma), accounting for ~50% of the detected subsidence, despite representing only 30% of the fire disturbed study area. Microtopography increased by 340% in this terrain unit as a result of ice wedge degradation. Increases in the frequency, magnitude, and severity of tundra fires will contribute to future thermokarst development and associated landscape change in Arctic tundra regions.

Analyzing the impacts of off-road vehicle (ORV) trails on watershed processes in Wrangell-St. Elias National Park and Preserve, Alaska.

Trails created by off-road vehicles (ORV) in boreal lowlands are known to cause local impacts, such as denuded vegetation, soil erosion, and permafrost thaw, but impacts on stream and watershed processes are less certain. In Wrangell-St. Elias National Park and Preserve (WRST), Alaska, ORV trails have caused local resource damage in intermountain lowlands with permafrost soils and abundant wetlands and there is a need to know whether these impacts are more extensive. Comparison of aerial photography from 1957, 1981, and 2004 coupled with ground surveys in 2009 reveal an increase in trail length and number and show an upslope expansion of a trail system around points of stream channel initiation. We hypothesized that these impacts could also cause premature initiation and headward expansion of channels because of lowered soil resistance and greater runoff accumulation as trails migrate upslope. Soil monitoring showed earlier and deeper thaw of the active layer in and adjacent to trails compared to reference sites. Several rainfall-runoff events during the summer of 2009 showed increased and sustained flow accumulation below trail crossings and channel shear forces sufficient to cause headward erosion of silt and peat soils. These observations of trail evolution relative to stream and wetland crossings together with process studies suggest that ORV trails are altering watershed processes. These changes in watershed processes appear to result in increasing drainage density and may also alter downstream flow regimes, water quality, and aquatic habitat. Addressing local land-use disturbances in boreal and arctic parklands with permafrost soils, such as WRST, where responses to climate change may be causing concurrent shifts in watershed processes, represents an important challenge facing resource managers.

Arctic lake physical processes and regimes with implications for winter water availability and management in the National Petroleum Reserve Alaska.

Lakes are dominant landforms in the National Petroleum Reserve Alaska (NPRA) as well as important social and ecological resources. Of recent importance is the management of these freshwater ecosystems because lakes deeper than maximum ice thickness provide an important and often sole source of liquid water for aquatic biota, villages, and industry during winter. To better understand seasonal and annual hydrodynamics in the context of lake morphometry, we analyzed lakes in two adjacent areas where winter water use is expected to increase in the near future because of industrial expansion. Landsat Thematic Mapper and Enhanced Thematic Mapper Plus imagery acquired between 1985 and 2007 were analyzed and compared with climate data to understand interannual variability. Measured changes in lake area extent varied by 0.6% and were significantly correlated to total precipitation in the preceding 12 months (p < 0.05). Using this relation, the modeled lake area extent from 1985 to 2007 showed no long-term trends. In addition, high-resolution aerial photography, bathymetric surveys, water-level monitoring, and lake-ice thickness measurements and growth models were used to better understand seasonal hydrodynamics, surface area-to-volume relations, winter water availability, and more permanent changes related to geomorphic change. Together, these results describe how lakes vary seasonally and annually in two critical areas of the NPRA and provide simple models to help better predict variation in lake-water supply. Our findings suggest that both overestimation and underestimation of actual available winter water volume may occur regularly, and this understanding may help better inform management strategies as future resource use expands in the NPRA.

Analysis of sediment retention in western riverine wetlands: the Yampa River watershed, Colorado, USA.

We quantified annual sediment deposition, bank erosion, and sediment budgets in nine riverine wetlands that represented a watershed continuum for 1 year in the unregulated Yampa River drainage basin in Colorado. One site was studied for 2 years to compare responses to peak flow variability. Annual mean sediment deposition ranged from 0.01 kg/m(2) along a first-order subalpine stream to 21.8 kg/m(2) at a sixth-order alluvial forest. Annual mean riverbank erosion ranged from 3 kg/m-of-bank at the first-order site to 1000 kg/m at the 6(th)-order site. Total sediment budgets were nearly balanced at six sites, while net export from bank erosion occurred at three sites. Both total sediment deposition (R(2) = 0.86, p < 0.01) and bank erosion (R(2) = 0.77, p < 0.01) were strongly related to bankfull height, and channel sinuosity and valley confinement helped to explain additional variability among sites. The texture and organic fraction of eroded and deposited sediment were relatively similar in most sites and varied among sites by watershed position. Our results indicate that bank erosion generally balances sediment deposition in riverine wetlands, and we found no distinct zones of sediment retention versus export on a watershed continuum. Zones of apparent disequilibrium can occur in unregulated rivers due to factors such as incised channels, beaver activity, and cattle grazing. A primary function of many western riverine wetlands is sediment exchange, not retention, which may operate by transforming materials and compounds in temporary sediment pools on floodplains. These results are considered in the context of the Hydrogeomorphic approach being implemented by the U.S. government for wetland resource management.