Sources of stream sulfate at the Hubbard Brook Experimental Forest: Long-term analyses using stable isotopes

Sulfur deposition in the northeastern U.S. has been decreasing since the 1970s and there has been a concomitant decrease in the SO42– lost from drainage waters from forest catchments of this region. It has been established previously that the SO42– lost from drainage waters exceeds SO42– inputs in bulk precipitation, but the cause for this imbalance has not been resolved. The use of stable S isotopes and the availability of archived bulk precipitation and stream water samples at the Hubbard Brook Experimental Forest (HBEF) in New Hampshire provided a unique opportunity to evaluate potential sources and sinks of S by analyzing the long-term patterns (1966–1994) of the 34S values of SO42–. In bulk precipitation adjacent to the Ecosystem Laboratory and near Watershed 6 the 34S values were greater (mean: 4.5 and 4.2l, respectively) and showed more variation (variance: 0.49 and 0.30) than stream samples from Watersheds 5 (W5) and 6 (W6) (mean: 3.2 and 3.7j; variance: 0.09 and 0.08, respectively). These results are consistent with other studies in forest catchments that have combined results for mass balances with stable S isotopes. These results indicate that for those sites, including the HBEF, where atmospheric inputs are 10 kg S ha–1 yr–1, most of the deposited SO42– cycles through the biomass before it is released to stream water. Results from W5, which had a whole-tree harvest in 1983–1984 showed that adsorption/desorption processes play an important role in regulating net SO42– retention for this watershed-ecosystem. Although the isotopic results suggest the importance of S mineralization, conclusive evidence that there is net mineralization has not yet been shown. However, S mass balances and the isotopic result are consistent with the mineralization of organic S being a major contributor to the SO42– in stream waters at the HBEF.     

Sulfate deposition and temperature controls on methane emission and sulfur forms in peat

Natural wetlands are the single most important contributors of methane (CH₄) to the atmosphere. Recent research has shown that the deposition of sulfate (SO ₄ ^2– ) can substantially reduce the emission of this radiatively important gas from wetlands. However, the influence of temperature in regulating the extent of this effect is unclear. Peatlands also constitute an important store of sulfur (S), so understanding the effect of S deposition on S dynamics within this store is important if we are to understand the interaction. The effect of enhanced SO ₄ ^2– deposition on CH₄ fluxes and S pools were investigated in peatland monoliths under controlled environment conditions. This enabled a close examination of effects at the onset of experimentally enhanced SO ₄ ^2– deposition while examining temperature effects on the interaction. Experimentally enhanced S deposition at rates as small as 15 kg SO ₄ ^2– -S ha^–1 year^–1 suppressed CH₄ emissions by 30%. There was no increased suppression at larger deposition rates of simulated acid rain. Temperature affected the suppressive effect of the simulated acid rain. At low temperatures (down to 5 °C), there was a greater proportional suppression than at higher temperatures (up to 20 °C). Evidence suggests that populations of SO ₄ ^2– -reducing bacteria do not respond, as previously thought, to enhanced SO ₄ ^2– supply with a boom followed by a bust and less recalcitrant S pools (SO ₄ ^2– and S°) were depleted in the SO ₄ ^2– -treated peat, indicating enhanced S turnover. A significant proportion of the SO ₄ ^2– from the treatment was taken up and stored as SO ₄ ^2– in vascular plants, placing this mechanism as a potentially important seasonal regulator of peatland SO ₄ ^2– availability.     

Processes affecting the response of sulfate concentrations to clearcutting in a northern hardwood forest, Catskill Mountains, New York, U.S.A.

The effects of disturbance on the biogeochemical processes that affect the sulfur (S) cycle in forested ecosystems are important, but have been studied in only a few locations. In this investigation, the mechanisms that caused large decreases in stream SO ₄ ^2– concentrations after clearcutting a small forested catchment in the Catskill Mountains of southeastern New York in 1997 were identified through an examination of pH and SO ₄ ^2– concentrations in soil solutions, bulk deposition of SO ₄ ^2– in throughfall collectors, adsorbed SO ₄ ^2– concentrations in buried soil bags, and spatial variations in SO ₄ ^2– concentrations in shallow groundwater. The load of SO ₄ ^2– –S in stream water during the first 2 years after clearcutting was about 2 kg ha^–1 year^–1 less than the background value of 8–10 kg ha^–1 year^–1. The 10 and 19% decrease in net throughfall flux of SO ₄ ^2– –S during the 2nd and 3rd year after the clearcut, respectively, reflects reduced dry deposition of S after removal of the canopy, but this decrease accounts for 0 and 43%, respectively, of the decrease in SO ₄ ^2– load in streamflow for these 2 years. The pH of B-horizon soil water decreased from 4.5 to 4.0 within 8 months after the clearcut, and SO ₄ ^2– concentrations decreased from 45 µmol L^–1 to less than 20 µmol L^–1 during this time. A strong correlation between SO ₄ ^2– concentrations and pH values (r ² = 0.71, p < 0.01) in B-horizon soil water during the post-harvest period (1997–1999) reflects increased SO ₄ ^2– adsorption in response to soil acidification. Sulfate concentrations in groundwater from 21 spatially distributed wells were inversely related to a topographic index that served as a surrogate for soil wetness; thus, providing additional evidence that SO ₄ ^2– adsorption was the dominant cause of the decreased SO ₄ ^2– concentrations in the stream after clearcutting. These results are consistent with those from a 1985 whole-tree harvest at the Hubbard Brook Experimental Forest in New Hampshire in which increased SO ₄ ^2– adsorption resulting from decreased soil pH was the primary cause of decreased SO ₄ ^2– concentrations in stream water.     

嗜酸硫杆菌属硫氧化系统研究进展

硫化矿的酸溶解和化学氧化过程中(H 和Fe3 作用下,金属硫化矿中分解),伴随着硫元素转变成多聚硫S8或硫代硫酸盐的过程。对嗜酸硫杆菌属硫氧化过程的研究表明,胞外环状多聚硫S8可能通过细胞外膜蛋白巯基活化成线状-SnH后,被转运到细胞周质区域,进而被硫加双氧酶氧化成SO32-,活化过程中同时生成少量H2S;这些酶促反应不需要辅助因子参与,不释放电子。胞外硫代硫酸盐通过未知途径进入细胞周质。细胞周质中的SO32-主要经由亚硫酸-受体氧化还原酶氧化成SO42-,S2O32-可能经由硫代硫酸盐-辅酶Q氧化还原酶、硫代硫酸盐脱氢酶、连四硫酸盐水解酶等氧化为硫酸,少量H2S则经由硫化物-辅酶Q氧化还原酶氧化为多聚硫,后者再经由SO32-和S2O32-氧化生成最后产物SO42-。这些生物氧化过程释放的电子进入呼吸链参与产生细菌生长代谢所需的能量。然而,关于A.ferrooxidans硫氧化系统中各种硫化合物的酶催化氧化机制的研究仍很缺乏,胞内外硫化合物的转运机制、是否存在胞外酶催化氧化等仍然有待解决。另外,硫的型态和价态、酶催化反应的细胞微区域以及硫氧化系统中一些关键酶的分离及其表达基因的鉴定等问题都还有待进一步研究。基于对这些事实的分析,提出了一个嗜酸硫杆菌属硫氧化系统的模型。     

Patterns of stable S isotopes in a forested catchment as indicators for biological S turnover

Despite intensive biogeochemical research during the last thirty years, the relative importance of biological S turnover for the overall SO ₄ ^2– budget of forested catchments remains uncertain. The objective of the present study was (i) to gain new insight into the S cycle of theLehstenbach catchment (Northeastern Bavaria, Germany) through the analysis of stable isotopes of S and (ii) to differentiate between sites which are hot spots for SO ₄ ^2– reduction and sites where mineralization and adsorption/desorption processes are more important. The ³⁴S values and SO ₄ ^2– concentrations of soil solutions, throughfall and groundwater at four different sites as well as runoff of the catchment were measured. The relatively low variability of ³⁴S in throughfall and bulk precipitation was in contrast to the high temporal and spatial variability of ³⁴S in the soil solution. Sulfate in the soil solution of upland sites was slightly depleted in³⁴S compared to input values. This was most likely due to S mineralization. Sulfate in the soil solution from wetland soils was clearly enriched in³⁴S, indicating dissimilatory SO ₄ ^2– reduction. The observed spatial and temporal patterns of³⁴S turnover and SO ₄ ^2– concentrations might explain the overall balanced S budget of the catchment. At a time of decreasing anthropogenic deposition SO ₄ ^2– is currently released from upland soils. Furthermore, mineralization of organic S may contribute to SO ₄ ^2– release. Wetland soils in the catchment represent a sink for SO ₄ ^2– due to dissimilatory SO ₄ ^2– reduction.     

Sulphate dynamics in a northern wetland catchment during snowmelt

Fluxes and stores of SO ₄ ^2– were measured in a small Canadian Shield basin during the 1989 snowmelt. Sulphate flux from the unsaturated zone (14.1 ± 7.3 kg ha^–1) was four times the amount supplied in meltwater and precipitation (3.5 ± 0.4 kg ha^–1). This reflects flushing of soluble S04- from organic and upper mineral soil horizons during melt, which counteracted potential dilution of groundwater SO ₄ ^2– levels by large water inputs to the basin. 35.6 ± 12.4 kg SO ₄ ^2– entered the saturated zone during melt, supplied equally by leaching from overlying soils and conversion of the capillary fringe to phreatic water due to rising water table levels. Streamflow conveyed 70% of the total SO ₄ ^2–1 export of 10.1 ± 2.3 kg ha^–1, and was largely supplied by groundwater discharge from a wotland in the lower portion of the basin. The remaining 30% of total export was via shallow subsurface flow. Results highlight the importance of unsaturated and saturated zone processes for SO ₄ ^2– dynamics and export during snowmelt.     

Transport of molybdate by Clostridium pasteurianum.

The transport of 99MoO42- into dinitrogen-fixing cells of Clostridium pasteurianum was investigated. Transport of molybdate in this organism is energy dependent; sucrose is required in the minimal media, and the system is inhibited by the glycolysis inhibitors, NaF, iodoacetic acid, and arsenate. The cells accumulate molybdate against a concentration gradient, and the uptake shows a marked dependence on temperature (optimum 37 C) and pH (optimum 6.0). The rate of molybdate uptake with increasing molybdate concentrations shows saturation kinetics with an apparent Km and Vmax of 4.8 X 10(-5) M and 55 nmol/g of dry cells per min, respectively. Inhibition studies with the anions SO42-, S2O32-, WO42-, and VO32- show that SO42- and WO42- competitively inhibit MoO42- uptake (apparent Ki [SO42-] is 3.0 X 10(-5) M; apparent Ki [WO42-] is 2.4 X 10(-5), whereas S2O32- and VO32- have no inhibitory effect. Exchange experiments with MoO42- show that only a small percentage of the 99MoO42- taken up by the cells is exchangeable. Exchange experiments with WO42- and SO42- indicate that once inside the cells WO42- and SO42- cannot substitute for MoO42-.     

A comparison of oxygen,nitrate, and sulfate respiration in coastal marine sediments

Aerobic respiration with oxygen and anaerobic respiration with nitrate (denitrification) and sulfate (sulfate reduction) were measured during winter and summer in two coastal marine sediments (Denmark). Both aerobic respiration and denitrification took place in the oxidized surface layer, whereas sulfate reduction was most significant in the deeper, reduced sediment. The low availability of nitrate apparently limited the activity of denitrification during summer to less than 0.2 mmoles NO ₃ ^– m^–2 day^–1, whereas activities of 1.0–3.0 mmoles NO ₃ ^– m^–2 day^–1 were measured during winter. Sulfate reduction, on the contrary, increased from 2.6–7.6 mmoles SO ₄ ^2– m^–2 day^–1 during winter to 9.8–15.1 mmoles SO ₄ ^2– m^–2 day^–1 during summer. The aerobic respiration was high during summer, 135–140 mmoles O₂ m^–2 day^–1, as compared to estimated winter activities of about 30 mmoles O₂ m^–2 day^–1. The little importance of denitrification relative to aerobic respiration and sulfate reduction is discussed in relation to the availability and distribution of oxygen, nitrate, and sulfate in the sediments and to the detritus mineralization.     

Models of sulfur dynamics in forest and grassland ecosystems with emphasis on soil processes

The major S constituents in terrestrial ecosystems include inorganic SO ₄ ^2– , C-bonded S and ester sulfate with the organic fractions constituting the major soil S pools. Conceptual models of S dynamics link inorganic SO ₄ ^2– flux to organic sulfur transformations and other elements such as N and C. Mass balance models have been useful in ascertaining whether a system is at steady-state with respect to adsorption processes and/or nutritional demands of vegetation for S. Chemical equilibrium/surface complexation models have been used to evaluate the effects of a complex of factors, including effects of pH on SO₄ ^– adsorption and precipitation; these models have not generally been integrated into ecosystem models of S dynamics. Models such as ILWAS, Birkenes, Storgama, Trickle-Down and MAGIC were developed to ascertain surface water acidification processes within watersheds; these models incorporated SO₄ ^2– adsorption in some formulation combined with hydrological considerations. None of these models explicitly treat organic S transformations and fluxes. In contrast, grassland ecosystem models detail organic S transformations, but give little attention to adsorption and hydrologic factors. More detailed simulation models of S transformations in forest and grassland soils have recently been developed, but these results have yet to be incorporated into ecosystem and watershed models.     

Combustion losses of sulphur from conifer foliage: Implications of chemical form and soil nitrogen status

The proportion of total sulphur lost during combustion (600 °C) of Douglas-fir (Pseudotsuga menziesii) foliage is reduced from> 90% to 65–70% as the SO₄-S concentration increases from 10% to 45–50% of the total S content. Foliar SO₄-S content is decreased by improvement of plant nitrogen status, suggesting that alterations to soil N availability may influence S transfer to the atmosphere during biomass burning.     

Episodic sulphate export from wetlands in acidified headwater catchments: prediction at the landscape scale

Sulphate (SO ₄ ^–2 ) concentrations in 34 intensively measured Canadian Shield streams near the Dorset Research Centre, central Ontario, were used to test a hydrogeologic model that uses simple measures of wetland area and till depth to identify catchments that produce SO ₄ ^–2 pulses. Mean annual measured maximum SO ₄ ^–2 concentrations were significantly greater in shallow till (<1 m depth) catchments containing wetlands than catchments covered with deeper tills (>1 m depth) containing wetlands or catchments with no wetlands. Average maximum SO ₄ ^–2 concentrations in wetland catchments during years with dry summers were >20 mg/L in 19 of 20 catchments with average till depths of <1 m, whereas concentrations were <20 mg/L in 5 of 6 watersheds with average till depths of >1 m. Peaks in mean annual maximum SO ₄ ^–2 concentrations from wetland catchments with shallow till occurred during summers with rain fall 150–200 mm less than potential evaporation estimates. There were no significant differences in mean average annual SO ₄ ^–2 concentration among the different catchments during wet summers, with SO ₄ ^–2 concentrations ranging from 6 to 13 mg/L. These observations suggest that a large portion of the temporal and spatial variation in SO ₄ ^–2 chemistry and export can be predicted in headwater catchments of the Canadian Shield and perhaps in other landscapes where till depth influences upland-wetland hydrologic connections.     

Microbial sulfate reduction with acetate: process performance and composition of the bacterial communities in the reactor at different salinity levels

Microbial sulfate reduction with acetate as carbon source and electron donor was investigated at salinity levels between 0.53 and 1.48%. The experiment was carried out in a 2.3-1 upflow anaerobic sludge blanket reactor inoculated with granular methanogenic sludge. A pH of 8.3, a temperature of 32 +/- 1 degrees C and a chemical oxygen demand (COD)/SO4(2-)-S ratio of 2 were maintained in the reactor throughout the experiment. Sulfate reduction and the composition of the dominant bacterial communities in the reactor were monitored. The results showed that a maximal conversion rate for SO4(2-)-S of 14 g l(-1) day(-1) and a conversion efficiency of more than 90% were obtained at a salinity level of 1.26-1.39%. A further increase in the salinity level led to reactor instability. Denaturant gradient gel electrophoresis of 16S rDNA fragments amplified by PCR from total bacterial DNA extracted from the inoculum and reactor sludge showed that salinity level had an impact on the composition of the bacterial communities in the reactor. However, no clear relationship was found between reactor performance and the composition of the dominant bacterial communities in the reactor.     

The iron-sulphur proteins: Evolution of a ubiquitous protein from model systems to higher organisms

Ferredoxins are Fe–S proteins with low molecular weight (6–12000) which act as electron carriers at very low redox potentials eg. –300 to –500 mV, in diverse biochemical processes such as bacterial and plant photosynthesis, N₂ fixation, carbon metabolism, oxidative phosphorylation and steroid hydroxylation. They are found in a wide range of organisms from the primitive obligate anaerobic bacteria, through photosynthetic bacteria, blue-green and green algae, to all higher plants and animals. Three types of ferredoxins are known –8 Fe+8 S, 4 Fe+4 S and 2 Fe+2 S. All three have been found in bacteria while the 2 Fe and some 8 Fe ferredoxins have been found in plants and animals possibly representing an evolutionary sequence. The 8 Fe ferredoxin may all be composed of two 4 Fe units. We have proposed that because of the simplicity of the 8 Fe ferredoxins (only 9 common simple amino acids in clostridia, 6 of which have been detected in the Murchison meteorite) they may have been amongst the earliest proteins formed during the origin of life. A simple peptide of about 27 amino acids could incorporate inorganic Fe+S (or possibly an existing Fe–S complex) into it nonenzymatically under anaerobic conditions to form a protein carrying one or two electrons at the potential of the H₂ electrode. More than ten Fe–S model compounds have been proposed as analogues of the 4 Fe or 2 Fe containing active centres; inorganic, organometallic and peptide complexes have been synthesized. A few have many of the properties of ferredoxins but none as yet fulfills a sufficient number of criteria to substitute for ferredoxins chemically and biologically — a goal which will provide many clues to primitive peptide systems undergoing biological electron transfer reactions.     

Desulfurella multipotens sp. nov., a new sulfur-respiring thermophilic eubacterium from Raoul Island (Kermadec archipelago,New Zealand)

A new moderately thermophilic sulfur-reducing eubacterium was isolated from bottom deposits of Green Lake (Raoul Island, Kermadec archipelago, New Zealand). Cells are short rods, 1.5–1.8 by 0.5–0.7 m, single or in pairs, motile with one polar flagellum, gram-negative with S-layer of subunit structure. Growth occurred between 42 and 77°C with the optimum at 58–60°C and at pH from 6.0 to 7.2 with the optimum at 6.4–6.8. The bacterium was obligately anaerobic and obligately sulfur-respiring, and capable of lithoautotrophic growth on a mineral medium with S° and H₂/CO₂ gas phase. In addition to molecular hydrogen, a wide range of substrates can be utilized as energy source in the presence of elemental sulfur: pyruvate, acetate, butyrate, pentadecanate, palmitate, stearate. Products are CO₂ and H₂S. The G+C content of DNA is 33.5 mol%. DNA-DNA homology with the type species of the genus Desulfurella — Desulfurella acetivorans — is 69±2%. A new species, Desulfurella multipotens sp. nov., with the type strain RH-8 is described.     

Reduction of sulfur by spirillum 5175 and syntrophism with Chlorobium.

A small spirillum, designated 5175, was isolated from an anaerobic enrichment culture for Desulfuromonas in which the major medium constituents were acetate and elemental sulfur. The organisms grew only under anaerobic or microaerophilic conditions. Elemental sulfur was formed anaerobically in a malate-sulfide medium, and cell densities of 10(8) cells/ml were obtained. Hydrogen and formate were actively oxidized as substrates for growth under anaerobic conditions; S0, S032-, or S2O32-, but not SO42-, served as electron acceptors and were stoichiometrically reduced to sulfide. Malate or fumarate likewise served as electron acceptors and were reduced to succinate. Nutritional requirements were simple, no vitamins or amino acids being required. For growth in inorganic media when carbon dioxide was the only carbon source, the addition of acetate was required as a source of cell carbon. The organism is gram negative. Cells had a diameter of 0.5 mum and a wavelength of 5.0 mum. Cell suspensions exhibited an absorption spectrum indicative of a cytochrome with peaks in the reduced form at 552, 523, and 416 nm. Well growing syntrophic cultures with Chlorobium were established with formate as the substrate.     

Kv Channel S1-S2 Linker Working as a Binding Site of Human β-Defensin 2 for Channel Activation Modulation

Among the three extracellular domains of the tetrameric voltage-gated K⁺ (Kv) channels consisting of six membrane-spanning helical segments named S1–S6, the functional role of the S1-S2 linker still remains unclear because of the lack of a peptide ligand. In this study, the Kv1.3 channel S1-S2 linker was reported as a novel receptor site for human β-defensin 2 (hBD2). hBD2 shifts the conductance-voltage relationship curve of the human Kv1.3 channel in a positive direction by nearly 10.5 mV and increases the activation time constant for the channel. Unlike classical gating modifiers of toxin peptides from animal venoms, which generally bind to the Kv channel S3-S4 linker, hBD2 only targets residues in both the N and C termini of the S1-S2 linker to influence channel gating and inhibit channel currents. The increment and decrement of the basic residue number in a positively charged S4 sensor of Kv1.3 channel yields conductance-voltage relationship curves in the positive direction by ∼31.2 mV and 2–4 mV, which suggests that positively charged hBD2 is anchored in the channel S1-S2 linker and is modulating channel activation through electrostatic repulsion with an adjacent S4 helix. Together, these findings reveal a novel peptide ligand that binds with the Kv channel S1-S2 linker to modulate channel activation. These findings also highlight the functional importance of the Kv channel S1-S2 linker in ligand recognition and modification of channel activation.     

Longitudinal and seasonal patterns of stream acidity in a headwater catchment on the Appalachian Plateau, West Virginia, U.S.A.

The chemical composition during baseflow was used to elucidate the fundamental processes controlling longitudinal and seasonal patterns of stream acidity in Yellow Creek, a chronically acidic headwater (pH range 3.7--4.2) on the Appalachian Plateau in northeastern West Virginia. Sulfate concentrations controlled the variability of stream acidity within the Yellow Creek catchment. Decreases in stream free H⁺ acidity with decreasing elevation likely resulted from SO ₄ ^2– retention in riparian wetland areas as well as spatial variation in dominant tree species. Seasonal variations in free H⁺ and inorganic monomeric aluminum (Alⁿ⁺) concentrations appeared related to seasonal fluctuations in baseflow discharge which was controlled by vegetative activity. Baseflow stream discharge, as well as H⁺ and Alⁿ⁺ acidity, gradually declined during the growing season (June through October), likely reflecting microbial SO ₄ ^2– > reduction in saturated anaerobic environments within riparian wetlands. A marked pulse of stream H⁺, Alⁿ⁺, and SO ₄ ^2– coincided with an abrupt increase in baseflow discharge resulting from the cessation of transpiration after leaf-fall in November. This seasonal pattern suggests that autumn may be a critical period for eastern brook trout in streams draining wetlands on the Appalachian Plateau.     

Stable isotope fractionation by Clostridium pasteurianum. 2. Regulation of sulfite reductases by sulfur amino acids and their influence on sulfur isotope fractionation during SO32- and SO42- reduction

In addition to an assimilatory sulfite reductase, studies of cultures of Clostridium pasteurianum supplemented with methionine, cysteine, and 35SO42- provides evidence for another reductase which is induced by SO32-. This inducible reductase appears to be dissimaltory because of the copious sulfide production arising when the cells are grown on SO32-. Cysteine can repress the assimilatory sulfite reductase but does not affect the inducible reductase. During late logarithmic growth on 1 mM SO42- + 10mM cysteine, depression of the inducible reductase occurred along with increased sulfide production. The presence of 1 mM cysteine and (or) 1 mM cysteine and (or) 1 mM methionine does not affect the inverse sulfur isotope effect for evolved H2S. However, 5 and 10 mM cysteine reduce the maximum delta34S value for released H2S from +40 to 10%. A small conversion of cysteine to H2S by C. pasteurianum occurs, but only in the stationary phase.     

Creating Novel Activated Factor XI Inhibitors through Fragment Based Lead Generation and Structure Aided Drug Design

Activated factor XI (FXIa) inhibitors are anticipated to combine anticoagulant and profibrinolytic effects with a low bleeding risk. This motivated a structure aided fragment based lead generation campaign to create novel FXIa inhibitor leads. A virtual screen, based on docking experiments, was performed to generate a FXIa targeted fragment library for an NMR screen that resulted in the identification of fragments binding in the FXIa S1 binding pocket. The neutral 6-chloro-3,4-dihydro-1H-quinolin-2-one and the weakly basic quinolin-2-amine structures are novel FXIa P1 fragments. The expansion of these fragments towards the FXIa prime side binding sites was aided by solving the X-ray structures of reported FXIa inhibitors that we found to bind in the S1-S1’-S2’ FXIa binding pockets. Combining the X-ray structure information from the identified S1 binding 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment and the S1-S1’-S2’ binding reference compounds enabled structure guided linking and expansion work to achieve one of the most potent and selective FXIa inhibitors reported to date, compound 13, with a FXIa IC₅₀ of 1.0 nM. The hydrophilicity and large polar surface area of the potent S1-S1’-S2’ binding FXIa inhibitors compromised permeability. Initial work to expand the 6-chloro-3,4-dihydro-1H-quinolin-2-one fragment towards the prime side to yield molecules with less hydrophilicity shows promise to afford potent, selective and orally bioavailable compounds.     

Concentration and flux of solutes from snow and forest floor during snowmelt in the West-Central Adirondack region of New York

Decreases in pH and increases in the concentration of Al and NO ₃ ^– have been observed in surface waters draining acid-sensitive regions in the northeastern U.S. during spring snowmelt. To assess the source of this acidity, we evaluated solute concentrations in snowpack, and in meltwater collected from snow and forest floor lysimeters in the west-central Adirondack Mountains of New York during the spring snowmelt period, 29 March through 15 April 1984.During the initial phase of snowmelt, ions were preferentially leached from the snowpack resulting in elevated concentrations in snowmelt water (e.g. H⁺ = 140 eq.l^–1; NO ₄ ^2– = 123 eq.l^–1; SO ₃ ^– = 160 eq.l^–1). Solute concentrations decreased dramatically within a few days of the initial melt (< 50 eq.l^–1). The concentrations of SO ₄ ^2– and NO ₃ ^– in snowpack and snowmelt water were similar, whereas NO^– ₃ in the forest floor leachate was at least two times the concentration of SO ₄ ^2– .Study results suggest that the forest floor was a sink for snowmelt inputs of alkalinity, and a net source of H⁺, NO ₃ ^– , dissolved organic carbon, K⁺ and Al inputs to the mineral soil. The forest floor was relatively conservative with respect to snowmelt inputs of Ca²⁺, SO ₄ ^2– and Cl^–. These results indicate that mineralization of N, followed by nitrification in the forest floor may be an important process contributing to elevated concentrations of H⁺ and NO ₃ ^– in streams during the snowmelt period.