Search

SuppFigure3. Stable suppression of PKM2 expression in G55 cells significantly alters intra-cellular concentrations of pyruvate and lactate. (*, p

Improvements in air quality have led to ecosystem recovery from acidic deposition, but the mechanisms and trajectories of this recovery are not fully understood. Here, we present long-term stream response and recovery data for paired watersheds at the Bear Brook Watershed in Maine (BBWM) during declining ambient SO4 and NO3 in precipitation. East Bear (EB) received ambient deposition from 1989 to 2018; West Bear (WB) received artificially elevated N + S from 1989 to 2016. The WB treatment was discontinued after 2016, the beginning of the recovery from both the experimental N + S and ambient decline. Stream SO4 in WB gradually declined after the treatment ended, from ~147 μeq L−1 in 2010–16 to ~126 μeq L−1 in 2017–18. The declining S inputs induced desorption of SO4 from soil phase surfaces, with stream loss far exceeding precipitation input. At the current rate of recovery, it will be many decades before the WB stream returns to pre-treatment SO4 concentrations. In contrast, NO3 is only weakly adsorbed in soil, and WB stream NO3 concentrations rapidly declined from ~39 μeq L−1 in 2010–16 to ~5 μeq L−1 in 2017–18, comparable to the N-limited EB stream. The acid anions are strongly coupled to base cation chemistry in streams, and there was a distinct hysteretic response of Ca and Mg to the chronic acidification, as (Ca + Mg) increased rapidly during the initial years, followed by declining values due to depletion of the soil exchange complex. This 30-year monitoring study (1989–2019) provides insights into recovery mechanisms from acidic deposition and highlights the role of abiotic processes in soil that mediate nutrient cycling and retention. Documenting the rapid response of N alongside the slower recovery for S identifies the temporal resolution necessary for other whole-watershed recovery studies.

We conducted a national-scale assessment of mercury (Hg) bioaccumulation in aquatic ecosystems, using dragonfly larvae as biosentinels, by developing a citizen-science network to facilitate biological sampling. Implementing a carefully designed sampling methodology for citizen scientists, we developed an effective framework for a landscape-level inquiry that might otherwise be resource limited. We assessed the variation in dragonfly Hg concentrations across >450 sites spanning 100 United States National Park Service units and examined intrinsic and extrinsic factors associated with the variation in Hg concentrations. Mercury concentrations ranged between 10.4 and 1411 ng/g dry weight across sites and varied among habitat types. Dragonfly total Hg (THg) concentrations were up to 1.8-fold higher in lotic habitats than in lentic habitats and 37% higher in waterbodies with abundant wetlands along their margins than those without wetlands. Mercury concentrations in dragonflies differed among families but were correlated (r2 > 0.80) with each other, enabling adjustment to a consistent family to facilitate spatial comparisons among sampling units. Dragonfly THg concentrations were positively correlated with THg concentrations in both fish and amphibians from the same locations, indicating that dragonfly larvae are effective indicators of Hg bioavailability in aquatic food webs. We used these relationships to develop an integrated impairment index of Hg risk to aquatic ecosytems and found that 12% of site-years exceeded high or severe benchmarks of fish, wildlife, or human health risk. Collectively, this continental-scale study demonstrates the utility of dragonfly larvae for estimating the potential mercury risk to fish and wildlife in aquatic ecosystems and provides a framework for engaging citizen science as a component of landscape Hg monitoring programs.

Mercury (Hg) is a toxic pollutant, widespread in northeastern U.S. ecosystems. Resource managers’ efforts to develop fish consumption advisories for humans and to focus conservation efforts for fish-eating wildlife are hampered by spatial variability. Dragonfly larvae can serve as biosentinels for Hg given that they are widespread in freshwaters, long-lived, exhibit site fidelity, and bioaccumulate relatively high mercury concentrations, mostly as methylmercury (88% ±11% MeHg in this study). We sampled lake water and dragonfly larvae in 74 northeastern US lakes that are part of the U.S. EPA Long-Term Monitoring Network, including 45 lakes in New York, 43 of which are in the Adirondacks. Aqueous dissolved organic carbon (DOC) and total Hg (THg) were strongly related to MeHg in lake water. Dragonfly larvae total mercury ranged from 0.016–0.918 μg/g, dw across the study area; Adirondack lakes had the minimum and maximum concentrations. Aqueous MeHg and dragonfly THg were similar between the Adirondack and Northeast regions, but a majority of lakes within the highest quartile of dragonfly THg were in the Adirondacks. Using landscape, lake chemistry, and lake morphometry data, we evaluated relationships with MeHg in lake water and THg in dragonfly larvae. Lakewater DOC and lake volume were strong predictors for MeHg in water. Dragonfly THg Bioaccumulation Factors (BAFs, calculated as [dragonfly THg]:[aqueous MeHg]) increased as lake volume increased, suggesting that lake size influences Hg bioaccumulation or biomagnification. BAFs declined with increasing DOC, supporting a potential limiting effect for MeHg bioavailability with higher DOC.

“Weather whiplash” is a colloquial phrase for describing an extreme event that includes shifts between two opposing weather conditions. Prior media coverage and research on these types of extremes have largely ignored winter weather events. However, rapid swings in winter weather can result in crossing from frozen to unfrozen conditions, or vice versa; thus, the potential impact of these types of events on coupled human and natural systems may be large. Given rapidly changing winter conditions in seasonally snow‐covered regions, there is a pressing need for a deeper understanding of such events and the extent of their impacts to minimize their risks. Here we introduce the concept of winter weather whiplash, defined as a class of extreme event in which a collision of unexpected conditions produces a forceful, rapid, back‐and‐forth change in winter weather that induces an outsized impact on coupled human and natural systems. Using a series of case studies, we demonstrate that the effects of winter weather whiplash events depend on the natural and human context in which they occur, and discuss how these events may result in the restructuring of social and ecological systems. We use the long‐term hydrometeorological record at the Hubbard Brook Experimental Forest in New Hampshire, USA to demonstrate quantitative methods for delineating winter weather whiplash events and their biophysical impacts. Ultimately, we argue that robust conceptual and quantitative frameworks for understanding winter weather whiplash events will contribute to the ways in which we mitigate and adapt to winter climate change in vulnerable regions.

Objective The Recruitment Innovation Center (RIC), partnering with the Trial Innovation Network and institutions in the National Institutes of Health-sponsored Clinical and Translational Science Awards (CTSA) Program, aimed to develop a service line to retrieve study population estimates from electronic health record (EHR) systems for use in selecting enrollment sites for multicenter clinical trials. Our goal was to create and field-test a low burden, low tech, and high-yield method. Materials and Methods In building this service line, the RIC strove to complement, rather than replace, CTSA hubs’ existing cohort assessment tools. For each new EHR cohort request, we work with the investigator to develop a computable phenotype algorithm that targets the desired population. CTSA hubs run the phenotype query and return results using a standardized survey. We provide a comprehensive report to the investigator to assist in study site selection. Results From 2017 to 2020, the RIC developed and socialized 36 phenotype-dependent cohort requests on behalf of investigators. The average response rate to these requests was 73%. Discussion Achieving enrollment goals in a multicenter clinical trial requires that researchers identify study sites that will provide sufficient enrollment. The fast and flexible method the RIC has developed, with CTSA feedback, allows hubs to query their EHR using a generalizable, vetted phenotype algorithm to produce reliable counts of potentially eligible study participants. Conclusion The RIC’s EHR cohort assessment process for evaluating sites for multicenter trials has been shown to be efficient and helpful. The model may be replicated for use by other programs.

The Bear Brook Watershed in Maine (BBWM) is a long‐term research site established to study the response of forest ecosystem function to environmental disturbances of chronic acidic deposition and ecosystem nitrogen enrichment. Starting in 1989, the West Bear (treated) watershed received bimonthly applications of ammonium sulfate [(NH₄)₂SO₄] fertilizer from above the canopy, whereas East Bear (reference) received ambient deposition. The treatments were stopped in 2016, marking the beginning of the recovery phase. Research at the site has focused on soils, streams, and vegetation. Here, we describe data collected over three decades at the BBWM—input and stream output nutrient fluxes, quantitative soil pits and soil chemistry, and soil temperature and moisture.

Magnetic resonance spectroscopic imaging (MRSI) offers considerable promise for monitoring metabolic alterations associated with disease or injury; however, to date, these methods have not had a significant impact on clinical care, and their use remains largely confined to the research community and a limited number of clinical sites. The MRSI methods currently implemented on clinical MRI instruments have remained essentially unchanged for two decades, with only incremental improvements in sequence implementation. During this time, a number of technological developments have taken place that have already greatly benefited the quality of MRSI measurements within the research community and which promise to bring advanced MRSI studies to the point where the technique becomes a true imaging modality, while making the traditional review of individual spectra a secondary requirement. Furthermore, the increasing use of biomedical MR spectroscopy studies has indicated clinical areas where advanced MRSI methods can provide valuable information for clinical care. In light of this rapidly changing technological environment and growing understanding of the value of MRSI studies for biomedical studies, this article presents a consensus from a group of experts in the field that reviews the state-of-the-art for clinical proton MRSI studies of the human brain, recommends minimal standards for further development of vendor-provided MRSI implementations, and identifies areas which need further technical development.

Clinical trials continue to face significant challenges in participant recruitment and retention. The Recruitment Innovation Center (RIC), part of the Trial Innovation Network (TIN), has been funded by the National Center for Advancing Translational Sciences of the National Institutes of Health to develop innovative strategies and technologies to enhance participant engagement in all stages of multicenter clinical trials. In collaboration with investigator teams and liaisons at Clinical and Translational Science Award institutions, the RIC is charged with the mission to design, field-test, and refine novel resources in the context of individual clinical trials. These innovations are disseminated via newsletters, publications, a virtual toolbox on the TIN website, and RIC-hosted collaboration webinars. The RIC has designed, implemented, and promised customized recruitment support for 173 studies across many diverse disease areas. This support has incorporated site feasibility assessments, community input sessions, recruitment materials recommendations, social media campaigns, and an array of study-specific suggestions. The RIC’s goal is to evaluate the efficacy of these resources and provide access to all investigating teams, so that more trials can be completed on time, within budget, with diverse participation, and with enough accrual to power statistical analyses and make substantive contributions to the advancement of healthcare.

PURPOSE To compare the performance of an 8-channel surface coil/clamshell transmitter and 32-channel head array coil/birdcage transmitter for hyperpolarized 13 C brain metabolic imaging. METHODS To determine the field homogeneity of the radiofrequency transmitters, B1 + mapping was performed on an ethylene glycol head phantom and evaluated by means of the double angle method. Using a 3D echo-planar imaging sequence, coil sensitivity and noise-only phantom data were acquired with the 8- and 32-channel receiver arrays, and compared against data from the birdcage in transceiver mode. Multislice frequency-specific 13 C dynamic echo-planar imaging was performed on a patient with a brain tumor for each hardware configuration following injection of hyperpolarized [1-13 C]pyruvate. Signal-to-noise ratio (SNR) was evaluated from pre-whitened phantom and temporally summed patient data after coil combination based on optimal weights. RESULTS The birdcage transmitter produced more uniform B1 + compared with the clamshell: 0.07 versus 0.12 (fractional error). Phantom experiments conducted with matched lateral housing separation demonstrated 8- versus 32-channel mean transceiver-normalized SNR performance: 0.91 versus 0.97 at the head center; 6.67 versus 2.08 on the sides; 0.66 versus 2.73 at the anterior; and 0.67 versus 3.17 on the posterior aspect. While the 8-channel receiver array showed SNR benefits along lateral aspects, the 32-channel array exhibited greater coverage and a more uniform coil-combined profile. Temporally summed, parameter-normalized patient data showed SNRmean,slice ratios (8-channel/32-channel) ranging 0.5-2.00 from apical to central brain. White matter lactate-to-pyruvate ratios were conserved across hardware: 0.45 ± 0.12 (8-channel) versus 0.43 ± 0.14 (32-channel). CONCLUSION The 8- and 32-channel hardware configurations each have advantages in particular brain anatomy.

Proton Magnetic Resonance Spectroscopy ((1)H MRS) provides non-invasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Whilst most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges towards obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the popular point resolved spectroscopy (PRESS) localization sequence was found to be unacceptably high at 3T, and the use of the semi-adiabatic localization by adiabatic selective refocusing (semi-LASER) sequence is a recommended solution. The incorporation of simulated metabolite basis-sets into analysis routines is recommended for reliably capturing the full spectral detail available from short echo time acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B(0)) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. We anticipate the implementation of these recommendations will strengthen current clinical applications and advance progress towards developing and validating new MRS biomarkers for clinical use.

Little is known about the regional extent and variability of nitrate from atmospheric deposition that is transported to streams without biological processing in forests. We measured water chemistry and isotopic tracers (δ18O and δ15N) of nitrate sources across the Northern Forest Region of the U.S. and Canada and reanalyzed data from other studies to determine when, where, and how unprocessed atmospheric nitrate was transported in catchments. These inputs were more widespread and numerous than commonly recognized, but with high spatial and temporal variability. Only 6 of 32 streams had high fractions (>20%) of unprocessed atmospheric nitrate during baseflow. Seventeen had high fractions during stormflow or snowmelt, which corresponded to large fractions in near-surface soil waters or groundwaters, but not deep groundwater. The remaining 10 streams occasionally had some (

This white paper discusses prospects for advancing hyperpolarization technology to better understand cancer metabolism, identify current obstacles to HP (hyperpolarized) 13C magnetic resonance imaging’s (MRI’s) widespread clinical use, and provide recommendations for overcoming them. Since the publication of the first NIH white paper on hyperpolarized 13C MRI in 2011, preclinical studies involving [1-13C]pyruvate as well a number of other 13C labeled metabolic substrates have demonstrated this technology's capacity to provide unique metabolic information. A dose-ranging study of HP [1-13C]pyruvate in patients with prostate cancer established safety and feasibility of this technique. Additional studies are ongoing in prostate, brain, breast, liver, cervical, and ovarian cancer. Technology for generating and delivering hyperpolarized agents has evolved, and new MR data acquisition sequences and improved MRI hardware have been developed. It will be important to continue investigation and development of existing and new probes in animal models. Improved polarization technology, efficient radiofrequency coils, and reliable pulse sequences are all important objectives to enable exploration of the technology in healthy control subjects and patient populations. It will be critical to determine how HP 13C MRI might fill existing needs in current clinical research and practice, and complement existing metabolic imaging modalities. Financial sponsorship and integration of academia, industry, and government efforts will be important factors in translating the technology for clinical research in oncology. This white paper is intended to provide recommendations with this goal in mind.

The Dragonfly Mercury Project (DMP) is a dynamic national scale program coupling scientific efforts to understand mercury pollution risks to protected areas with citizen engagement and education. W...

The vernal transition represents the seasonal transition to spring, occurring as temperatures rise at the end of winter. With rapid snowmelt, microbial community turnover, and accelerated nutrient cycling, this is a critical but relatively under-studied period of ecosystem function. We conducted a study over two consecutive winters (2015-2016) at the Bear Brook Watershed in Maine to examine how changing winter conditions (warming winters, reduced snow accumulation) altered soil nitrogen availability and stream N export during winter and the vernal transition, and how these patterns were influenced by ecosystem N status (N-enriched vs. N-limited). Of the two study years, 2016 had a warmer winter with substantially less snow accumulation and a discontinuous snowpack-and as a result, had a longer vernal transition and a snowpack that thawed before the vernal transition began. Across both years, snowmelt triggered a transition, signaled by increased ammonium concentrations in soil, decreased soil nitrate concentrations due to flushing by meltwater, and increased stream nitrate exports. Despite the contrasting winter conditions, both years showed similar patterns in N availability and export, differing only in the timing of these transitions. The vernal transition has conventionally been considered a critical period for biogeochemical cycling, because the associated snowmelt event triggers physicochemical and biochemical changes in soil systems. This was consistent with our results in 2015, but our data for 2016 show that this may not always hold true, and instead, that warmer, low-snow winters may demonstrate a temporal asynchrony between snowmelt and the vernal transition. We also show that ecosystem N status is a strong driver of the seasonal N pattern, and the interaction of N status and changing climate must be further investigated to understand ecosystem function under our current predicted trajectory of warming winters, declining snowfall, and winter thaw events.

The vernal transition represents the seasonal transition to spring, occurring as temperatures rise at the end of winter. With rapid snowmelt, microbial community turnover, and accelerated nutrient cycling, this is a critical but relatively under-studied period of ecosystem function. We conducted a study over two consecutive winters (2015-2016) at the Bear Brook Watershed in Maine to examine how changing winter conditions (warming winters, reduced snow accumulation) altered soil nitrogen availability and stream N export during winter and the vernal transition, and how these patterns were influenced by ecosystem N status (N-enriched vs. N-limited). Of the two study years, 2016 had a warmer winter with substantially less snow accumulation and a discontinuous snowpack-and as a result, had a longer vernal transition and a snowpack that thawed before the vernal transition began. Across both years, snowmelt triggered a transition, signaled by increased ammonium concentrations in soil, decreased soil nitrate concentrations due to flushing by meltwater, and increased stream nitrate exports. Despite the contrasting winter conditions, both years showed similar patterns in N availability and export, differing only in the timing of these transitions. The vernal transition has conventionally been considered a critical period for biogeochemical cycling, because the associated snowmelt event triggers physicochemical and biochemical changes in soil systems. This was consistent with our results in 2015, but our data for 2016 show that this may not always hold true, and instead, that warmer, low-snow winters may demonstrate a temporal asynchrony between snowmelt and the vernal transition. We also show that ecosystem N status is a strong driver of the seasonal N pattern, and the interaction of N status and changing climate must be further investigated to understand ecosystem function under our current predicted trajectory of warming winters, declining snowfall, and winter thaw events.

BackgroundDifferentiating treatment-induced injury from recurrent high-grade glioma is an ongoing challenge in neuro-oncology, in part due to lesion heterogeneity. This study aimed to determine whether different MR features were relevant for distinguishing recurrent tumor from the effects of treatment in contrast-enhancing lesions (CEL) and non-enhancing lesions (NEL).MethodsThis prospective study analyzed 291 tissue samples (222 recurrent tumor, 69 treatment-effect) with known coordinates on imaging from 139 patients who underwent preoperative 3T MRI and surgery for a suspected recurrence. 8 MR parameter values were tested from perfusion-weighted, diffusion-weighted, and MR spectroscopic imaging at each tissue sample location for association with histopathological outcome using generalized estimating equation models for CEL and NEL tissue samples. Individual cutoff values were evaluated using receiver operating characteristic curve analysis with 5-fold cross-validation.ResultsIn tissue samples obtained from CEL, elevated relative cerebral blood volume (rCBV) was associated with the presence of recurrent tumor pathology (P < 0.03), while increases in normalized choline (nCho) and choline-to-NAA index (CNI) were associated with the presence of recurrent tumor pathology in NEL tissue samples (P < 0.008). A mean CNI cutoff value of 2.7 had the highest performance, resulting in mean sensitivity and specificity of 0.61 and 0.81 for distinguishing treatment-effect from recurrent tumor within the NEL.ConclusionAlthough our results support prior work that underscores the utility of rCBV in distinguishing the effects of treatment from recurrent tumor within the contrast enhancing lesion, we found that metabolic parameters may be better at differentiating recurrent tumor from treatment-related changes in the NEL of high-grade gliomas.

Climate change in northeastern North America is resulting in warmer winters with reduced snow accumulation. Soils under a thin snowpack are more likely to experience freeze–thaw cycles, disrupting carbon (C) and nitrogen (N) transformations. We conducted a 2 year snow removal experiment in Maine to study the effects of soil freezing on soil C and N processes. O horizon soils were sampled during winter and spring of 2015 and 2016, and they were analyzed for labile inorganic N and water-extractable organic carbon (WEOC) concentrations, specific ultraviolet absorbance (SUVA254), and potential net N mineralization. The winter of 2015 was cold and snowy, whereas 2016 was warm with a shallow, short-term snowpack. Snow removal caused the soils to freeze, but winter rain-on-soil events in 2015 resulted in the formation of concrete frost, as opposed to granular frost in 2016. Concrete frost increased soil ammonium (NH4+-N) and WEOC concentrations and decreased SUVA254, which we attribute to microbial cell lysis. In contrast, granular frost did not alter soil nutrient concentrations, reflecting limited microbial distress. Our study demonstrates that moisture content influences the intensity of soil freezing, highlighting the importance of snowpack depth and winter rain events in regulating winter and spring biogeochemical processes and nutrient availability.

The USA has set aside over 400 national parks and other protected areas to be managed by the National Park Service (NPS). Collectively, these sites attract over 300 million visits per year which makes the NPS one of the largest informal education institutions in the country. Because the NPS supports and facilitates scientific studies in parks, the national park system provides abundant opportunity for biologists and other scientists to engage global audiences in learning, exploring, and even conducting science. Those opportunities are best pursued through collaborations among scientists and the professional communication staff (interpreters, educators, media specialists, etc.) of parks and their partner organizations. This article describes unique opportunities and rationale for such collaborations, presents several examples that highlight the range of activities and lessons drawn from them, and invites scientists to conduct studies in parks and bring their science into the public eye.