NLRP3 Inflammasome Inhibitors for Antiepileptogenic Drug Discovery and Development.

Epilepsy is one of the most prevalent and serious brain disorders and affects over 70 million people globally. Antiseizure medications (ASMs) relieve symptoms and prevent the occurrence of future seizures in epileptic patients but have a limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with the Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms of these medications for the development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made, and challenges faced in the development of NLRP3 inhibitors for the treatment of epilepsy.

Distribution and trends of mercury in aquatic and terrestrial biota of New York, USA: a synthesis of 50 years of research and monitoring.

Mercury (Hg) inputs have particularly impacted the northeastern United States due to its proximity to anthropogenic emissions sources and abundant habitats that efficiently convert inorganic Hg into methylmercury. Intensive research and monitoring efforts over the past 50 years in New York State, USA, have informed the assessment of the extent and impacts of Hg exposure on fishes and wildlife. By synthesizing Hg data statewide, this study quantified temporal trends of Hg exposure, spatiotemporal patterns of risk, the role that habitat and Hg deposition play in producing spatial patterns of Hg exposure in fish and other wildlife, and the effectiveness of current monitoring approaches in describing Hg trends. Most temporal trends were stable, but we found significant declines in Hg exposure over time in some long-sampled fish. The Adirondack Mountains and Long Island showed the greatest number of aquatic and terrestrial species with elevated Hg concentrations, reflecting an unequal distribution of exposure risk to fauna across the state. Persistent hotspots were detected for aquatic species in central New York and the Adirondack Mountains. Elevated Hg concentrations were associated with open water, forests, and rural, developed habitats for aquatic species, and open water and forested habitats for terrestrial species. Areas of consistently elevated Hg were found in areas driven by atmospheric and local Hg inputs, and habitat played a significant role in translating those inputs into biotic exposure. Continued long-term monitoring will be important in evaluating how these patterns continue to change in the face of changing land cover, climate, and Hg emissions.

All about oxygen: using near-infrared spectroscopy to understand bioenergetics.

The interchange among the energy-providing phosphagen, glycolytic, and aerobic systems during exercise is often poorly understood by beginning students in exercise physiology. Exercise is oftentimes thought of as being aerobic or anaerobic, with the body progressing sequentially from one system to the next, although the energy systems work synergistically to produce energy from the onset of exercise, and all ultimately use oxygen. Traditional methods of teaching these concepts using only indirect calorimetry and a metabolic cart can be misleading. Relatively inexpensive noninvasive monitors of muscle oxygenation levels ([Formula: see text]) provide a useful tool to help students better understand the contribution and timing of these three systems of ATP generation and convey the concept that ultimately all energy production in the human body is oxygen dependent. In this laboratory, students use near-infrared spectroscopy (NIRS) to visualize oxygen utilization by skeletal muscle during exercise by devising three exercise unique protocols, with each designed to stress a different energy system. Students then perform their protocols while using NIRS to measure and analyze [Formula: see text]. Students generate graphs with collected data, allowing them to visualize and appreciate oxygen consumption during all three protocols as well as elevated oxygen consumption after exercise. The students learn that any exercise is really all about oxygen.NEW & NOTEWORTHY Traditional methods of teaching bioenergetics using indirect calorimetry and a metabolic cart may be misleading. Recent advances in technology have made near-infrared spectroscopy (NIRS) a relatively inexpensive, noninvasive means of monitoring muscle oxygen levels during exercise. In this laboratory activity, NIRS devices are used for hands-on exploration of the synergistic nature of the energy systems, allowing students to appreciate the synergistic nature of the energy systems and how all exercise is really all about oxygen.

Atmospheric nitrogen deposition in the Chesapeake Bay watershed: A history of change.

The Chesapeake Bay watershed has been the focus of pioneering studies of the role of atmospheric nitrogen (N) deposition as a nutrient source and driver of estuarine trophic status. Here, we review the history and evolution of scientific investigations of the role of atmospheric N deposition, examine trends from wet and dry deposition networks, and present century-long (1950-2050) atmospheric N deposition estimates. Early investigations demonstrated the importance of atmospheric deposition as an N source to the Bay, providing 25%-40% among all major N sources. These early studies led to the unprecedented inclusion of targeted decreases in atmospheric N deposition as part of the multi-stakeholder effort to reduce N loads to the Bay. Emissions of nitrogen oxides (NOx) and deposition of wet nitrate, oxidized dry N, and dry ammonium ( NH 4 + ) sharply and synchronously declined by 60%-73% during 1995-2019. These decreases largely resulted from implementation of Title IV of the 1990 Clean Air Act Amendments, which began in 1995. Wet NH 4 + deposition shows no significant trend during this period. The century-long atmospheric N deposition estimates indicate an increase in total atmospheric N deposition in the Chesapeake watershed from 1950 to a peak of ~15 kg N/ha/yr in 1979, trailed by a slight decline of <10% through the mid-1990s, and followed by a sharp decline of about 40% thereafter through 2019. An additional 21% decline in atmospheric N deposition is projected from 2015 to 2050. A comparison of the Potomac River and James River watersheds indicates higher atmospheric N deposition in the Potomac, likely resulting from greater emissions from higher proportions of agricultural and urban land in this basin. Atmospheric N deposition rose from 30% among all N sources to the Chesapeake Bay watershed in 1950 to a peak of 40% in 1973, and a decline to 28% by 2015. These data highlight the important role of atmospheric N deposition in the Chesapeake Bay watershed and present a potential opportunity for decreases in deposition to contribute to further reducing N loads and improving the trophic status of tidal waters.

The response of streams in the Adirondack region of New York to projected changes in sulfur and nitrogen deposition under changing climate.

Modeling studies project that in the future surface waters in the northeast US will continue to recover from acidification over decades following reductions in atmospheric sulfur dioxide and nitrogen oxides emissions. However, these studies generally assume stationary climatic conditions over the simulation period and ignore the linkages between soil and surface water recovery from acid deposition and changing climate, despite fundamental impacts to watershed processes and comparable time scales for both phenomena. In this study, the integrated biogeochemical model PnET-BGC was applied to two montane forest watersheds in the Adirondack region of New York, USA to evaluate the recovery of surface waters from historical acidification in response to possible future changes in climate and atmospheric sulfur and nitrogen deposition. Statistically downscaled climate scenarios on average project warmer temperatures and greater precipitation for the Adirondack by the end of the century. Model simulations suggest under constant climate, acid-sensitive Buck Creek would gain 12.8 µeq L-1 of acid neutralizing capacity (ANC) by 2100 from large reductions in deposition, whereas acid insensitive Archer Creek is projected to gain 7.9 µeq L-1 of ANC. However, climate change could limit those improvements in acid-base status. Under climate change, a negative offset relative to the ANC increases with no climate change are projected for both streams by 2100. In acid-insensitive Archer Creek the negative offset (-8.5 µeq L-1) was large enough that ANC is projected to decrease by -0.6 µeq L-1, whereas in acid-sensitive Buck Creek, the negative offset (-0.4 µeq L-1) resulted in a slight decline of the projected future ANC increase to 12.4 µeq L-1. Calculated target loads for 2150 for both sites decreased when future climate change was considered in model simulations, which suggests further reductions in acid deposition may be necessary to restore ecosystem structure and function under a changing climate.

The impact of lime additions on mercury dynamics in stream chemistry and macroinvertebrates: a comparison of watershed and direct stream addition management strategies.

Acid deposition has declined across eastern North America and northern Europe due to reduced emissions of sulfur and nitrogen oxides. Ecosystem recovery has been slow with limited improvement in surface water chemistry. Delayed recovery has encouraged acid-neutralization strategies to accelerate recovery of impaired biological communities. Lime application has been shown to increase pH and dissolved organic carbon (DOC), which could also drive increased mobilization of mercury (Hg) to surface waters. A four-year study was conducted within Honnedaga Lake's watershed in the Adirondack region of New York to compare the effects of watershed and direct channel lime additions on Hg in stream water and macroinvertebrates. All treatments sharply increased stream pH and DOC concentrations, but large differences in the duration of impacts were apparent. The watershed treatment resulted in multi-year increases in concentrations and loads of total Hg (150%; 390%), DOC (190%; 350%) and nutrients, whereas total Hg and DOC increased for short periods (72-96 h) after channel treatments. No response of Hg in macroinvertebrates was evident following the watershed treatment, but a potential short-term and spatially constrained increase occurred after the channel treatment. Our observations indicate that both treatment approaches mobilize Hg, but that direct channel liming mobilizes considerably less than watershed liming over any period longer than a few days. During the final study year, increased methyl Hg concentrations were observed across reference and treated streams, which may reflect an extended dry period, highlighting that climate variation may also affect Hg dynamics.

Mercury in fish from streams and rivers in New York State: Spatial patterns, temporal changes, and environmental drivers.

Mercury (Hg) concentrations in freshwater fish across the state of New York frequently exceed guidelines considered harmful to humans and wildlife, but statewide distribution and temporal changes are not well known for the state's streams and rivers. We analyzed existing data to describe recent spatial patterns, identify key environmental drivers, and assess temporal changes. Size classes within sportfishes and prey fishes formed 'functional taxa' (FT), and standardized scores were generated from 2007-2016 data for 218 sites. Muscle Hg in ≥1 sportfish FT exceeded human-health guidelines of 50 ng/g (sensitive populations) and 300 ng/g (general population, GP) at 93 and 56% of sites, respectively, but exceeded 1000 ng/g (a state threshold) at only 10% of sites. Whole-body Hg in ≥1 prey fish FT exceeded wildlife thresholds of 40 ng/g and 100 ng/g at 91 and 51% of sites, respectively. Environmental drivers of recent spatial patterns include extent of forest cover and storage, the latter an indicator of wetlands. Standardized Hg scores increased with increasing atmospheric Hg deposition and storage across rural 'upland' regions of New York. However, scores were not related to atmospheric deposition in more-developed 'lowland' regions due to the limited methylation potential of urban landscapes. Comparisons of 2010-2015 sportfish Hg concentrations with those of 1998 and 2000-2005 showed inconsistent temporal changes both among and within eight sites examined. Some recent stream and river fish Hg spatial patterns differed from those of lake-based studies, highlighting the importance of New York's flowing waters to future Hg monitoring and risk assessment.

Demographic Profile and Service-Connection Trends of Posttraumatic Stress Disorder and Traumatic Brain Injury in US Veterans Pre- and Post-9/11.

INTRODUCTION: This study seeks to understand the demographic changes in the active-duty service member profile, both prior to and following September 11, 2001 (9/11). The study analyzed diagnosis of posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) and measures of severity of those diagnoses as recorded in service-connection ratings (percent disability). METHODS: A retrospective cohort-study of military veterans who received care at Veterans Health Administration medical centers between December 1998 and May 2014 was conducted based on clinical data recorded and stored within the Corporate Data Warehouse. RESULTS: A cohort of 1,339,937 veterans received an inpatient or outpatient diagnosis of PTSD and/or TBI. The cohort was divided into 4 service period groups and 3 diagnosis categories. The service periods included pre-9/11 (n = 1,030,806; 77%), post-9/11 (n = 204,083; 15%), overlap-9/11 (n = 89,953; 7%), and reentered post-9/11 (n = 15,095; 1%). The diagnosis categories included PTSD alone (n = 1,132,356; 85%), TBI alone (n = 100,789; 7%) and PTSD+TBI (n = 106,792; 8%). Results of the post-9/11 group revealed significant changes, including (1) increase of veterans with PTSD+TBI; (2) increase of female veterans with PTSD+TBI; and (3) increase of severity level of diagnosed PTSD/TBI as evidenced by higher service-connected disability pensions at younger age in the post-9/11 group. Additionally, data revealed unequal distribution of veterans with PTSD+TBI across geographic areas. CONCLUSIONS: The veteran of the post-9/11 service period does not mirror the veteran of the pre-9/11 service period. Findings are valuable for policy making, allocation of resources, and for reconsidering the prevailing paradigm for treating veterans with PTSD and/or TBI.

The response of stream ecosystems in the Adirondack region of New York to historical and future changes in atmospheric deposition of sulfur and nitrogen.

The present-day acid-base chemistry of surface waters can be directly linked to contemporary observations of acid deposition; however, pre-industrial conditions are key to predicting the potential future recovery of stream ecosystems under decreasing loads of atmospheric sulfur (S) and nitrogen (N) deposition. The integrated biogeochemical model PnET-BGC was applied to 25 forest watersheds that represent a range of acid sensitivity in the Adirondack region of New York, USA to simulate the response of streams to past and future changes in atmospheric S and N deposition, and calculate the target loads of acidity for protecting and restoring stream water quality and ecosystem health. Using measured data, the model was calibrated and applied to simulate soil and stream chemistry at all study sites. Model hindcasts indicate that historically stream water chemistry in the Adirondacks was variable, but inherently sensitive to acid deposition. The median model-simulated acid neutralizing capacity (ANC) of the streams was projected to be 55 µeq L-1 before the advent of anthropogenic acid deposition (~1850), decreasing to minimum values of 10 µeq L-1 around the year 2000. The median simulated ANC increased to 13 µeq L-1 by 2015 in response to decreases in acid deposition that have occurred over recent decades. Model projections suggest that simultaneous decreases in sulfate, nitrate and ammonium deposition are more effective in restoring stream ANC than individual decreases in sulfur or nitrogen deposition. However, the increases in stream ANC per unit equivalent decrease in S deposition is greater compared to decreases in N deposition. Using empirical algorithms, fish community density and biomass are projected to increase under several deposition-control scenarios that coincide with increases in stream ANC. Model projections suggest that even under the most aggressive deposition-reduction scenarios, stream chemistry and fisheries will not fully recover from historical acidification by 2200.

A synthesis of ecosystem management strategies for forests in the face of chronic nitrogen deposition.

Total nitrogen (N) deposition has declined in many parts of the U.S. and Europe since the 1990s. Even so, it appears that decreased N deposition alone may be insufficient to induce recovery from the impacts of decades of elevated deposition, suggesting that management interventions may be necessary to promote recovery. Here we review the effectiveness of four remediation approaches (prescribed burning, thinning, liming, carbon addition) on three indicators of recovery from N deposition (decreased soil N availability, increased soil alkalinity, increased plant diversity), focusing on literature from the U.S. We reviewed papers indexed in the Web of Science since 1996 using specific key words, extracted data on the responses to treatment along with ancillary data, and conducted a meta-analysis using a three-level variance model structure. We found 69 publications (and 2158 responses) that focused on one of these remediation treatments in the context of N deposition, but only 29 publications (and 408 responses) reported results appropriate for our meta-analysis. We found that carbon addition was the only treatment that decreased N availability (effect size: -1.80 to -1.84 across metrics), while liming, thinning, and prescribed burning all tended to increase N availability (effect sizes: +0.4 to +1.2). Only liming had a significant positive effect on soil alkalinity (+10.5%-82.2% across metrics). Only prescribed burning and thinning affected plant diversity, but with opposing and often statistically marginal effects across metrics (i.e., increased richness, decreased Shannon or Simpson diversity). Thus, it appears that no single treatment is effective in promoting recovery from N deposition, and combinations of treatments should be explored. These conclusions are based on the limited published data available, underscoring the need for more studies in forested areas and more consistent reporting suitable for meta-analyses across studies.

Unprocessed Atmospheric Nitrate in Waters of the Northern Forest Region in the U.S. and Canada.

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 (<20%) unprocessed atmospheric nitrate during stormflow or baseflow. Large, sporadic events may continue to be cryptic due to atmospheric deposition variation among storms and a near complete lack of monitoring for these events. A general lack of observance may bias perceptions of occurrence; sustained monitoring of chronic nitrogen pollution effects on forests with nitrate source apportionments may offer insights needed to advance the science as well as assess regulatory and management schemes.

Decreased atmospheric nitrogen deposition in eastern North America: Predicted responses of forest ecosystems.

Historical increases in emissions and atmospheric deposition of oxidized and reduced nitrogen (N) provided the impetus for extensive, global-scale research investigating the effects of excess N in terrestrial and aquatic ecosystems, with several regions within the Eastern Deciduous Forest of the United States found to be susceptible to negative effects of excess N. The Clean Air Act and associated rules have led to decreases in emissions and deposition of oxidized N, especially in eastern U.S., representing a research challenge and opportunity for ecosystem ecologists and biogeochemists. The purpose of this paper is to predict changes in the structure and function of North American forest ecosystems in a future of decreased N deposition. Hysteresis is a property of a system wherein output is not a strict function of corresponding input, incorporating lag, delay, or history dependence, particularly when the response to decreasing input is different from the response to increasing input. We suggest a conceptual hysteretic model predicting varying lag times in recovery of soil acidification, plant biodiversity, soil microbial communities, forest carbon (C) and N cycling, and surface water chemistry toward pre-N impact conditions. Nearly all of these can potentially respond strongly to reductions in N deposition. Most responses are expected to show some degree of hysteresis, with the greatest delays in response occurring in processes most tightly linked to "slow pools" of N in wood and soil organic matter. Because experimental studies of declines in N loads in forests of North America are lacking and because of the expected hysteresis, it is difficult to generalize from experimental results to patterns expected from declining N deposition. These will likely be long-term phenomena, difficult to distinguish from other, concurrent environmental changes, including elevated atmospheric CO2, climate change, reductions in acidity, invasions of new species, and long-term vegetation responses to past disturbance.

Stability of mercury concentration measurements in archived soil and peat samples.

Archived soil samples can provide important information on the history of environmental contamination and by comparison with recently collected samples, temporal trends can be inferred. Little previous work has addressed whether mercury (Hg) concentrations in soil samples are stable with long-term storage under standard laboratory conditions. In this study, we have re-analyzed using cold vapor atomic absorption spectroscopy a set of archived soil samples that ranged from relatively pristine mountainous sites to a polluted site near a non-ferrous metal smelter with a wide range of Hg concentrations (6.7-6485 µg kg-1). Samples included organic and mineral soils and peats with a carbon content that ranged from 0.2 to 47.7%. Soil samples were stored in polyethylene bags or bottles and held in laboratory rooms where temperature was not kept to a constant value. Mercury concentrations in four subsets of samples were originally measured in 2000, 2005, 2006 and 2007, and re-analyzed in 2017, i.e. after 17, 12, 11 and 10 years of storage. Statistical analyses of either separated or lumped data yielded no significant differences between the original and current Hg concentrations. Based on these analyses, we show that archived soil and peat samples can be used to evaluate historical soil mercury contamination.

Long-term Changes in Soil and Stream Chemistry across an Acid Deposition Gradient in the Northeastern United States.

Declines in acidic deposition across Europe and North America have led to decreases in surface water acidity and signs of chemical recovery of soils from acidification. To better understand the link between recovery of soils and surface waters, chemical trends in precipitation, soils, and streamwater were investigated in three watersheds representing a depositional gradient from high to low across the northeastern United States. Significant declines in concentrations of H (ranging from -1.2 to -2.74 microequivalents [µeq] L yr), NO (ranging from -0.6 to -0.84 µeq L yr), and SO (ranging from -0.95 to -2.13 µeq L yr) were detected in precipitation in the three watersheds during the period 1999 to 2013. Soil chemistry in the A horizon of the watershed with the greatest decrease in deposition showed significant decreases in exchangeable Al and increases in exchangeable bases. Soil chemistry did not significantly improve during the study in the other watersheds, and base saturation in the Oa and upper B horizons significantly declined in the watershed with the smallest decrease in deposition. Streamwater SO concentrations significantly declined in all three streams (ranging from -2.01 to -2.87 µeq L yr) and acid neutralizing capacity increased (ranging from 1.38 to 1.60 µeq L yr) in the two streams with the greatest decreases in deposition. Recovery of soils has likely been limited by decades of acid deposition that have leached base cations from soils with base-poor parent material.

Response of mercury in an Adirondack (NY, USA) forest stream to watershed lime application.

Surface waters in Europe and North America previously impacted by acid deposition are recovering in conjunction with declining precursor emissions since the 1980s. Lime has been applied to some impacted watersheds to accelerate recovery. The response to liming can be considered a proxy for future recovery from acid deposition. Increases in dissolved organic carbon concentrations have been observed in surface waters in response to increased pH associated with recovery from acid deposition. Although not previously described, recovery-related increases in dissolved organic carbon could drive increases in mercury concentrations and loads because of the affinity of mercury for dissolved organic matter. We used a before-after impact-response approach to describe the response of stream mercury cycling to the application of lime to the watershed of a small stream in the Adirondack Mountains of New York, USA. Dissolved organic carbon, total mercury and methylmercury concentrations increased significantly in streamwater within two weeks of treatment, to previously unobserved concentrations. After six months, post-treatment before-after impact-control (BACI) tests indicate that mean dissolved organic carbon concentrations and total mercury to dissolved organic carbon ratios remained significantly higher and limed site fluxes of methylmercury were lower than those at the reference stream. This pattern suggests total mercury is leaching at elevated levels from the limed watershed, but limitations in production and transport to the stream channel likely resulted in increases in methylmercury concentration that were of limited duration.

Watershed 'Chemical Cocktails': Forming Novel Elemental Combinations in Anthropocene Fresh Waters.

In the Anthropocene1, watershed chemical transport is increasingly dominated by novel combinations elements, which are hydrologically linked together as 'chemical cocktails.' Chemical cocktails are novel because human activities greatly enhance elemental concentrations and their probability for biogeochemical interactions and shared transport along hydrologic flowpaths. A new chemical cocktail approach advances our ability to: trace contaminant mixtures in watersheds, develop chemical proxies with high-resolution sensor data, and manage multiple water quality problems. We explore the following questions: (1) Can we classify elemental transport in watersheds as chemical cocktails using a new approach? (2) What is the role of climate and land use in enhancing the formation and transport of chemical cocktails in watersheds? To address these questions, we first analyze trends in concentrations of carbon, nutrients, metals, and salts in fresh waters over 100 years. Next, we explore how climate and land use enhance the probability of formation of chemical cocktails of carbon, nutrients, metals, and salts. Ultimately, we classify transport of chemical cocktails based on solubility, mobility, reactivity, and dominant phases: (1) sieved chemical cocktails (e.g., particulate forms of nutrients, metals and organic matter); (2) filtered chemical cocktails (e.g., dissolved organic matter and associated metal complexes); (3) chromatographic chemical cocktails (e.g., ions eluted from soil exchange sites); and (4) reactive chemical cocktails (e.g., limiting nutrients and redox sensitive elements). Typically, contaminants are regulated and managed one element at a time, even though combinations of elements interact to influence many water-quality problems such as toxicity to life, eutrophication, infrastructure and water treatment. A chemical cocktail approach significantly expands evaluations of water-quality signatures and impacts beyond single elements to mixtures. High-frequency sensor data (pH, specific conductance, turbidity, etc.) can serve as proxies for chemical cocktails and improve real-time analyses of water-quality violations, identify regulatory needs, and track water quality recovery following and extreme climate events. Ultimately, a watershed chemical cocktail approach is necessary for effectively co-managing groups of contaminants and provides a more holistic approach for studying, monitoring, and managing water quality in the Anthropocene.

The response of soil and stream chemistry to decreases in acid deposition in the Catskill Mountains, New York, USA.

The Catskill Mountains have been adversely impacted by decades of acid deposition, however, since the early 1990s, levels have decreased sharply as a result of decreases in emissions of sulfur dioxide and nitrogen oxides. This study examines trends in acid deposition, stream-water chemistry, and soil chemistry in the southeastern Catskill Mountains. We measured significant reductions in acid deposition and improvement in stream-water quality in 5 streams included in this study from 1992 to 2014. The largest, most significant trends were for sulfate (SO42-) concentrations (mean trend of -2.5 µeq L-1 yr-1); hydrogen ion (H+) and inorganic monomeric aluminum (Alim) also decreased significantly (mean trends of -0.3 µeq L-1 yr-1 for H+ and -0.1 µeq L-1 yr-1 for Alim for the 3 most acidic sites). Acid neutralizing capacity (ANC) increased by a mean of 0.65 µeq L-1 yr-1 for all 5 sites, which was 4 fold less than the decrease in SO42- concentrations. These upward trends in ANC were limited by coincident decreases in base cations (-1.3 µeq L-1 yr-1 for calcium + magnesium). No significant trends were detected in stream-water nitrate (NO3-) concentrations despite significant decreasing trends in NO3- wet deposition. We measured no recovery in soil chemistry which we attributed to an initially low soil buffering capacity that has been further depleted by decades of acid deposition. Tightly coupled decreasing trends in stream-water silicon (Si) (-0.2 µeq L-1 yr-1) and base cations suggest a decrease in the soil mineral weathering rate. We hypothesize that a decrease in the ionic strength of soil water and shallow groundwater may be the principal driver of this apparent decrease in the weathering rate. A decreasing weathering rate would help to explain the slow recovery of stream pH and ANC as well as that of soil base cations.

Modeled ecohydrological responses to climate change at seven small watersheds in the northeastern United States.

A cross-site analysis was conducted on seven diverse, forested watersheds in the northeastern United States to evaluate hydrological responses (evapotranspiration, soil moisture, seasonal and annual streamflow, and water stress) to projections of future climate. We used output from four atmosphere-ocean general circulation models (AOGCMs; CCSM4, HadGEM2-CC, MIROC5, and MRI-CGCM3) included in Phase 5 of the Coupled Model Intercomparison Project, coupled with two Representative Concentration Pathways (RCP 8.5 and 4.5). The coarse resolution AOGCMs outputs were statistically downscaled using an asynchronous regional regression model to provide finer resolution future climate projections as inputs to the deterministic dynamic ecosystem model PnET-BGC. Simulation results indicated that projected warmer temperatures and longer growing seasons in the northeastern United States are anticipated to increase evapotranspiration across all sites, although invoking CO2 effects on vegetation (growth enhancement and increases in water use efficiency (WUE)) diminish this response. The model showed enhanced evapotranspiration resulted in drier growing season conditions across all sites and all scenarios in the future. Spruce-fir conifer forests have a lower optimum temperature for photosynthesis, making them more susceptible to temperature stress than more tolerant hardwood species, potentially giving hardwoods a competitive advantage in the future. However, some hardwood forests are projected to experience seasonal water stress, despite anticipated increases in precipitation, due to the higher temperatures, earlier loss of snow packs, longer growing seasons, and associated water deficits. Considering future CO2 effects on WUE in the model alleviated water stress across all sites. Modeled streamflow responses were highly variable, with some sites showing significant increases in annual water yield, while others showed decreases. This variability in streamflow responses poses a challenge to water resource management in the northeastern United States. Our analyses suggest that dominant vegetation type and soil type are important attributes in determining future hydrological responses to climate change.

A new look at liming as an approach to accelerate recovery from acidic deposition effects.

Acidic deposition caused by fossil fuel combustion has degraded aquatic and terrestrial ecosystems in North America for over four decades. The only management option other than emissions reductions for combating the effects of acidic deposition has been the application of lime to neutralize acidity after it has been deposited on the landscape. For this reason, liming has been a part of acid rain science from the beginning. However, continued declines in acidic deposition have led to partial recovery of surface water chemistry, and the start of soil recovery. Liming is therefore no longer needed to prevent further damage, so the question becomes whether liming would be useful for accelerating recovery of systems where improvement has lagged. As more is learned about recovering ecosystems, it has become clear that recovery rates vary with watershed characteristics and among ecosystem components. Lakes appear to show the strongest recovery, but recovery in streams is sluggish and recovery of soils appears to be in the early stages. The method in which lime is applied is therefore critical in achieving the goal of accelerated recovery. Application of lime to a watershed provides the advantage of increasing Ca availability and reducing or preventing mobilization of toxic Al, an outcome that is beneficial to both terrestrial and aquatic ecosystems. However, the goal should not be complete neutralization of soil acidity, which is naturally produced. Liming of naturally acidic areas such as wetlands should also be avoided to prevent damage to indigenous species that rely on an acidic environment.

Evaluating the Safety of Somatic Periosteal Cells by Flow-Cytometric Analysis Monitoring the History of DNA Damage.

In preparing cell-based products for regenerative therapy, cell quality should be strictly controlled. Methodologies for evaluating cell viability, identity, and purity are established and used routinely, whereas current methodologies for evaluating cell safety, particularly genetic integrity or tumorigenicity, are time-consuming and relatively insensitive. As part of developing a more practical screening system, the authors previously demonstrated that γ-H2AX and p53 were useful markers for evaluating the history of DNA damage. To validate these markers further and develop a more quantitative methodology, single cell-based expression of these markers and two additional candidates have now been examined using flow cytometry (FCM). FCM analysis and immunofluorescent staining demonstrated that γ-ray-irradiation suppressed proliferation, enlarged cells, and cell nuclei, and immediately upregulated γ-H2AX and p21(waf1) in large numbers of cells for up to 12 days. Gamma-H2AX foci were formed in the nuclei of many affected cells. An initial sharp increase in p53 expression declined slowly over 12 days, while Rb expression increased linearly. The present findings suggest that this high-throughput, cell-based, combinational evaluation of protein markers and cell size enables a small number of cells with a history of DNA damage to be detected quickly and routinely from within a very large cell population. Using this screening methodology will improve the ability to verify the quality of cell-based products used in regenerative therapy.