The potential for tree planting strategies to reduce local and regional ecosystem impacts of agricultural ammonia emissions.

Trees are very effective at capturing both gaseous and particulate pollutants from the atmosphere. But while studies have often focussed on PM and NOx in the urban environment, little research has been carried out on the tree effect of capturing gaseous emissions of ammonia in the rural landscape. To examine the removal or scavenging of ammonia by trees a long-range atmospheric model (FRAME) was used to compare two strategies that could be used in emission reduction policies anywhere in the world where nitrogen pollution from agriculture is a problem. One strategy was to reduce the emission source strength of livestock management systems by implementing two 'tree-capture' systems scenarios - tree belts downwind of housing and managing livestock under trees. This emission reduction can be described as an 'on-farm' emission reduction policy, as ammonia is 'stopped' from dispersion outside the farm boundaries. The second strategy was to apply an afforestation policy targeting areas of high ammonia emission through two planting scenarios of increasing afforestation by 25% and 50%. Both strategies use trees with the aim of intercepting NH3 emissions to protect semi-natural areas. Scenarios for on-farm emission reductions showed national reductions in nitrogen deposition to semi-natural areas of 0.14% (0.2 kt N-NHx) to 2.2% (3.15 kt N-NHx). Scenarios mitigating emissions from cattle and pig housing gave the highest reductions. The afforestation strategy showed national reductions of 6% (8.4 kt N-NHx) to 11% (15.7 kt N-NHx) for 25% and 50% afforestation scenarios respectively. Increased capture by the planted trees also showed an added benefit of reducing long range effects including a decrease in wet deposition up to 3.7 kt N-NHx (4.6%) and a decrease in export from the UK up to 8.3 kt N-NHx (6.8%).

Development of a low-cost system for measuring conditional time-averaged gradients of SO2 and NH3.

A conditional time-averaged gradient (COTAG) system has been developed to provide direct long-term (weekly to monthly) average flux gradient measurements for a range of trace gases, between land and atmosphere. Over daily periods, atmospheric conditions can range from high stability, where the vertical gradients of ambient concentration are enhanced due to very small diffusivity, to highly unstable conditions, in which concentration gradients are small due to the intense turbulent activity of the surface layer. The large vertical gradients generated by high stability would bias the estimate of the actual flux: to avoid this, the COTAG system samples conditionally, within a carefully refined range of stability. A comparison with a continuous flux gradient system suggested that the removal of stable conditions from the sampling period does not substantially modify the evaluation of the long-term fluxes.

Accelerometer activity tracking in horses and the effect of pasture management on time budget.

BACKGROUND: Accelerometry is an accepted means of quantifying human physical activity. Quantitative physical activity tracking could be beneficial for studies into equine health and disease prevention, for example in relation to obesity management. OBJECTIVES: Validate accelerometer use in grazing horses, determine between-day repeatability, and assess the effects of pasture size on time budget (i.e. duration in each activity category). STUDY DESIGN: Proof of concept. METHODS: Accelerometers (ActiGraph) were positioned at the poll. Horses underwent 5 min of observed activity in three categories: standing, grazing and ambulating. Receiver-operating characteristic curve analysis, used on ten second data epochs, calculated cut points between the activities. A 20-day study was then undertaken on 6 horses at pasture. Time in each category (per day) was deduced; a Mann Whitney U test was performed to compare standard vs. small paddock and day vs. night turn out. RESULTS: Cut-off values with the optimum sensitivity (94.7-97.7%) and specificity (94.7-96.8%) were found to be <127.6 counts for standing, 127.6-702.7 counts for grazing and >702.7 counts for ambulating. Repeatability was analysed descriptively: Median (IQR) of the between-day difference in minutes standing, grazing and ambulating were 46.9 (21.3-87.9), 77.3 (40.2-124.5) and 15.6 (6.8-40.2) respectively. Median times standing and ambulating were significantly different between standard and small paddocks: standing: 8.7 vs. 10.3 h (P<0.001); ambulating: 55.7 vs. 39.6 min (P = 0.002). There was no significant difference in the median time spent grazing. There were significant differences between day and night: standing: 32.95% vs. 50.97% (P = 0.001), grazing: 60.81% vs. 46.77% (P<0.001) and ambulating: 4.57% vs. 2.40% (P<0.001). MAIN LIMITATIONS: Small sample size and lack of cross-validation of cut-off points on independent, 'unseen' data. CONCLUSIONS: Accelerometry can differentiate standing, grazing and ambulating in horses. Our proof-of-concept study demonstrates modifying pasture size influences activity budgets; opening avenues into studying obesity management.

δ15N of lichens reflects the isotopic signature of ammonia source.

Although it is generally accepted that δ15N in lichen reflects predominating N isotope sources in the environment, confirmation of the direct correlation between lichen δ15N and atmospheric δ15N is still missing, especially under field conditions with most confounding factors controlled. To fill this gap and investigate the response of lichens with different tolerance to atmospheric N deposition, thalli of the sensitive Evernia prunastri and the tolerant Xanthoria parietina were exposed for ten weeks to different forms and doses of N in a field manipulation experiment where confounding factors were minimized. During this period, several parameters, namely total N, δ15N and chlorophyll a fluorescence, were measured. Under the experimental conditions, δ15N in lichens quantitatively responded to the δ15N of released gaseous ammonia (NH3). Although a high correlation between the isotopic signatures in lichen tissue and supplied N was found both in tolerant and sensitive species, chlorophyll a fluorescence indicated that the sensitive species very soon lost its photosynthetic functionality with increasing N availability. The most damaging response to the different N chemical forms was observed with dry deposition of NH3, although wet deposition of ammonium ions had a significant observable physiological impact. Conversely, there was no significant effect of nitrate ions on chlorophyll a fluorescence, implying differential sensitivity to dry deposition versus wet deposition and to ammonium versus nitrate in wet deposition. Evernia prunastri was most sensitive to NH3, then NH4+, with lowest sensitivity to NO3-. Moreover, these results confirm that lichen δ15N can be used to indicate the δ15N of atmospheric ammonia, providing a suitable tool for the interpretation of the spatial distribution of NH3 sources in relation to their δ15N signal.

Parallel molecular pathways mediate expression of distinct forms of intermediate-term facilitation at tail sensory-motor synapses in Aplysia.

Three distinct temporal phases of synaptic facilitation (short-, intermediate-, and long-term) are induced by serotonin (5-HT) at sensory (SN) to motor (MN) synapses in Aplysia. Here, we characterize two mechanistically distinct forms of intermediate-term facilitation (ITF) at tail SN-MN synapses. One form, activity-independent ITF, is produced by five spaced pulses of 5-HT in the absence of SN activity. Its induction requires protein synthesis, and its expression requires persistent activation of PKA but not PKC. The other form, activity-dependent ITF, is produced by a single pulse of 5-HT coincident with SN activation. Its induction does not require protein synthesis, and its expression requires persistent activation of PKC but not PKA. These results demonstrate that SN-MN synapses can exhibit two distinct forms of ITF that are mediated by parallel molecular pathways.

Molecular mechanisms underlying a unique intermediate phase of memory in aplysia.

Short- and long-term synaptic facilitation induced by serotonin at Aplysia sensory-motor (SN-MN) synapses has been widely used as a cellular model of short- and long-term memory for sensitization. In recent years, a distinct intermediate phase of synaptic facilitation (ITF) has been described at SN-MN synapses. Here, we identify a novel intermediate phase of behavioral memory (ITM) for sensitization in Aplysia and demonstrate that it shares the temporal and mechanistic features of ITF in the intact CNS: (1) it declines completely prior to the onset of LTM, (2) its induction requires protein but not RNA synthesis, and (3) its expression requires the persistent activation of protein kinase A. Thus, in Aplysia, the same temporal and molecular characteristics that distinguish ITF from other phases of synaptic plasticity distinguish ITM from other phases of behavioral memory.

Strain field measurements on mouse carotid arteries using microscopic three-dimensional digital image correlation.

A stereomicroscope system is adapted to make accurate, quantitative displacement, and strain field measurements with microscale spatial resolution and nanoscale displacement resolution on mouse carotid arteries. To perform accurate and reliable calibration for these systems, a two-step calibration process is proposed and demonstrated using a modification to recently published procedures. Experimental results demonstrate that the microscope system with three-dimensional digital image correlation (3D-DIC) successfully measures the full 3D displacement and surface strain fields at the microscale during pressure cycling of 0.40-mm-diameter mouse arteries, confirming that the technique can be used to quantify changes in local biomechanical response which may result from variations in extracellular matrix composition, with the goal of quantifying properties of the vessel.

Stress responses of Calluna vulgaris to reduced and oxidised N applied under 'real world conditions'.

Effects and implications of reduced and oxidised N, applied under 'real world' conditions, since May 2002, are reported for Calluna growing on an ombrotrophic bog. Ammonia has been released from a 10 m line source generating monthly concentrations of 180-6 microg m(-3), while ammonium chloride and sodium nitrate are applied in rainwater at nitrate and ammonium concentrations below 4mM and providing up to 56 kg N ha(-1) year(-1) above a background deposition of 10 kg N ha(-1) year(-1). Ammonia concentrations, >8 microg m(-3) have significantly enhanced foliar N concentrations, increased sensitivity to drought, frost and winter desiccation, spring frost damage and increased the incidence of pathogen outbreaks. The mature Calluna bushes nearest the NH3 source have turned bleached and moribund. By comparison the Calluna receiving reduced and oxidised N in rain has shown no significant visible or stress related effects with no significant increase in N status.

Modelling the spatial distribution of ammonia emissions in the UK.

Ammonia emissions (NH3) are characterised by a high spatial variability at a local scale. When modelling the spatial distribution of NH3 emissions, it is important to provide robust emission estimates, since the model output is used to assess potential environmental impacts, e.g. exceedance of critical loads. The aim of this study was to provide a new, updated spatial NH3 emission inventory for the UK for the year 2000, based on an improved modelling approach and the use of updated input datasets. The AENEID model distributes NH3 emissions from a range of agricultural activities, such as grazing and housing of livestock, storage and spreading of manures, and fertilizer application, at a 1-km grid resolution over the most suitable landcover types. The results of the emission calculation for the year 2000 are analysed and the methodology is compared with a previous spatial emission inventory for 1996.

Uncertainties and implications of applying aggregated data for spatial modelling of atmospheric ammonia emissions.

Ammonia emissions vary greatly at a local scale, and effects (eutrophication, acidification) occur primarily close to sources. Therefore it is important that spatially distributed emission estimates are located as accurately as possible. The main source of ammonia emissions is agriculture, and therefore agricultural survey statistics are the most important input data to an ammonia emission inventory alongside per activity estimates of emission potential. In the UK, agricultural statistics are collected at farm level, but are aggregated to parish level, NUTS-3 level or regular grid resolution for distribution to users. In this study, the Modifiable Areal Unit Problem (MAUP), associated with such amalgamation, is investigated in the context of assessing the spatial distribution of ammonia sources for emission inventories. England was used as a test area to study the effects of the MAUP. Agricultural survey data at farm level (point data) were obtained under license and amalgamated to different areal units or zones: regular 1-km, 5-km, 10-km grids and parish level, before they were imported into the emission model. The results of using the survey data at different levels of amalgamation were assessed to estimate the effects of the MAUP on the spatial inventory. The analysis showed that the size and shape of aggregation zones applied to the farm-level agricultural statistics strongly affect the location of the emissions estimated by the model. If the zones are too small, this may result in false emission "hot spots", i.e., artificially high emission values that are in reality not confined to the zone to which they are allocated. Conversely, if the zones are too large, detail may be lost and emissions smoothed out, which may give a false impression of the spatial patterns and magnitude of emissions in those zones. The results of the study indicate that the MAUP has a significant effect on the location and local magnitude of emissions in spatial inventories where amalgamated, zonal data are used.

Challenges in quantifying biosphere-atmosphere exchange of nitrogen species.

Recent research in nitrogen exchange with the atmosphere has separated research communities according to N form. The integrated perspective needed to quantify the net effect of N on greenhouse-gas balance is being addressed by the NitroEurope Integrated Project (NEU). Recent advances have depended on improved methodologies, while ongoing challenges include gas-aerosol interactions, organic nitrogen and N(2) fluxes. The NEU strategy applies a 3-tier Flux Network together with a Manipulation Network of global-change experiments, linked by common protocols to facilitate model application. Substantial progress has been made in modelling N fluxes, especially for N(2)O, NO and bi-directional NH(3) exchange. Landscape analysis represents an emerging challenge to address the spatial interactions between farms, fields, ecosystems, catchments and air dispersion/deposition. European up-scaling of N fluxes is highly uncertain and a key priority is for better data on agricultural practices. Finally, attention is needed to develop N flux verification procedures to assess compliance with international protocols.

Long-term increases in soil carbon due to ecosystem fertilization by atmospheric nitrogen deposition demonstrated by regional-scale modelling and observations.

Fertilization of nitrogen (N)-limited ecosystems by anthropogenic atmospheric nitrogen deposition (Ndep) may promote CO2 removal from the atmosphere, thereby buffering human effects on global radiative forcing. We used the biogeochemical ecosystem model N14CP, which considers interactions among C (carbon), N and P (phosphorus), driven by a new reconstruction of historical Ndep, to assess the responses of soil organic carbon (SOC) stocks in British semi-natural landscapes to anthropogenic change. We calculate that increased net primary production due to Ndep has enhanced detrital inputs of C to soils, causing an average increase of 1.2 kgCm-2 (c. 10%) in soil SOC over the period 1750-2010. The simulation results are consistent with observed changes in topsoil SOC concentration in the late 20th Century, derived from sample-resample measurements at nearly 2000 field sites. More than half (57%) of the additional topsoil SOC is predicted to have a short turnover time (c. 20 years), and will therefore be sensitive to future changes in Ndep. The results are the first to validate model predictions of Ndep effects against observations of SOC at a regional field scale. They demonstrate the importance of long-term macronutrient interactions and the transitory nature of soil responses in the terrestrial C cycle.

Extinction training regulates tyrosine hydroxylase during withdrawal from cocaine self-administration.

Chronic exposure to drugs of abuse is known to modulate tyrosine hydroxylase (TH) levels in the mesolimbic dopamine system. In this study, 12 d of cocaine self-administration in rats (4 hr/d) reduced TH immunoreactivity by 29% in the nucleus accumbens (NAc) shell, but not core, after a 1 week withdrawal period. In contrast, TH immunoreactivity in the NAc was completely restored in animals that experienced extinction training (4 hr/d) during the same withdrawal period. Extinction training also increased TH levels in the ventral tegmental area (VTA) by 45%, whereas TH was not altered in the VTA by cocaine withdrawal alone. Thus, extinction-induced normalization of NAc TH levels could involve increased TH synthesis, stability, and/or transport from the VTA to the NAc. A similar extinction training regimen failed to alter TH levels in the NAc or VTA of rats trained to self-administer sucrose pellets, indicating that TH regulation in cocaine-trained animals is not a generalized effect of extinction learning per se. Rather, these data suggest that neuroadaptative responses during cocaine withdrawal ultimately are determined by a complex interaction between chronic drug exposure and drug-seeking experience. The ability of extinction training to restore NAc TH levels is hypothesized to accelerate recovery from dopamine depletion and anhedonia during cocaine withdrawal.

Factors that determine a propensity for cocaine-seeking behavior during abstinence in rats.

Individual differences in locomotor responses to novelty and psychostimulants, and sensitization following repeated drug exposure, predict increased sensitivity to the reinforcing effects of psychostimulants and are thought to underlie vulnerability to drug addiction. This study tested whether these factors determine another core feature of drug addiction, the propensity for drug-seeking behavior during abstinence in rats with prior cocaine-self-administration experience. Low and high response groups for each of these factors were determined in outbred rats by the median locomotor response to novelty and amphetamine prior to cocaine self-administration (pre-test), and to amphetamine during abstinence (post-test). Cocaine-seeking behavior during abstinence was measured by the level of drug-paired lever responding during extinction, and also during reinstatement induced by cocaine-associated cues, an amphetamine priming injection, and footshock stress. Animals with low and high locomotor responses to novelty and the amphetamine pre-test showed similar levels of cocaine-seeking behavior during extinction and reinstatement testing. Locomotor responses to amphetamine following cocaine self-administration (post-test) also failed to determine amphetamine's ability to reinstate cocaine-seeking behavior. Conversely, high levels of amphetamine-induced reinstatement were associated specifically with escalating cocaine intake during prior self-administration. These animals also developed locomotor sensitization to amphetamine following cocaine self-administration (post-test vs. pre-test), but the capacity to develop locomotor sensitization was not sufficient to determine a propensity for cocaine-seeking behavior. The findings suggest that the relationship between locomotor responses to novelty, amphetamine and behavioral sensitization a,nd the propensity for cocaine-seeking behavior during abstinence is complex, while the level of drug intake during prior self-administration is a primary determinant of this behavior.

A randomized, double-blind study of the effect of olestra on disease activity in patients with quiescent inflammatory bowel disease. Olestra in IBD Study Group.

PURPOSE: To determine the effects of olestra, a zero-calorie fat substitute that is neither digested nor absorbed, on the well-being and disease state of persons with chronic inflammatory bowel disease (IBD) in remission. PATIENTS AND METHODS: Eighty-nine patients with mild to moderate ulcerative colitis (n = 43) or Crohn's disease (n = 46) in remission, with a history of disease of 2 years or longer, were enrolled in this prospective study from nine private practices, three university-based medical centers, and one Veterans Administration medical center in the United States. Forty-four patients were randomly assigned to receive olestra and 45 to receive triglycerides in chips or cookies daily for 4 weeks. At Week 4, patients were classified as in remission, worsened, or relapsed according to an investigator's global assessment based on sigmoidoscopy (for ulcerative colitis) or the Crohn's disease activity index, laboratory findings, and clinical course. RESULTS: At Week 4, the olestra and triglyceride groups did not differ significantly with respect to the percentages of patients who relapsed (P = 0.494; difference = 2.4%; upper 95% CL = 8.8%) or with respect to the percentages of patients who experienced any worsening of their symptoms (P = 0.630; difference = 0.2%; upper 95% CL = 13.3%). Of evaluable patients, 90% (37 of 41) given olestra remained in remission with no worsening, compared with 90% (38 of 42) given triglycerides. Gastrointestinal symptoms were comparable between the treatment groups, and there were no treatment-related laboratory abnormalities. Six patients were excluded from analysis for reasons unrelated to treatment. CONCLUSION: Olestra did not affect the activity of quiescent mild to moderate IBD.

Psychopharmacology of conditioned reward: evidence for a rewarding signal at D1-like dopamine receptors.

A neutral stimulus can acquire conditioned rewarding properties through association with an intrinsically rewarding stimulus. The acquisition of responding for conditioned rewards requires that environmental stimuli and reward processes interact in a highly specific manner; analyses of this phenomenon may provide valuable insight into the processes that underlie reward-related learning. The effects of dopaminergic agents with different mechanisms of action in this paradigm have revealed several interesting dissociations suggesting that a rewarding signal at dopamine D1-like receptors may mediate both the acquisition of rewarding properties by neutral stimuli and their ability to control behavior. Dopamine-induced changes in responding for conditioned reward are susceptible to modulation by other neurotransmitter systems. In many cases, the molecular and cellular bases of these interactions support the notion that signaling through D1-like receptors is critical for a conditioned reward to direct responding. The model outlined in this paper reflects a comprehensive integration of the existing literature in the field, and has several implications that are readily testable by future research. Moreover, given the known biochemical coupling of D1-like receptors, this model may help in characterizing the sequence of intracellular events, from signal transduction to possible transcriptional and/or translational regulation, that give rise to the acquisition of rewarding properties by neutral stimuli.

Intracranial metastases as the first manifestation of prostate cancer.

We report on 2 patients with neurologic symptoms secondary to intracranial metastases from carcinoma of the prostate. In one of these patients, the intracranial lesion was the only clinically detectable metastasis. We have found only three other such cases reported in the English-language literature.

Adenovirus-mediated suicide gene therapy for experimental bladder cancer.

OBJECTIVES: To determine the feasibility, safety, and efficacy of suicide gene therapy using adenoviral-mediated herpes simplex virus thymidine kinase gene (HSV-tk) and the prodrug ganciclovir (GCV) in a murine model of human transitional cell carcinoma. METHODS: We used a replication-defective adenoviral construct containing the beta-galactosidase gene (ADV/Rous sarcoma virus [RSV]-beta-gal) as a control or ADV/RSV-tk as the therapeutic vector under the transcriptional control of the RSV long-terminal repeat promoter. Transduction efficiency was assessed in vitro by infection of MBT-2 cells with ADV/RSV-beta-gal at various multiplicities of infection (MOI) utilizing 5-bromo-4-chlor-3-indolyl-beta-D-galactoside (X-gal) staining. Sensitivity of MBT-2 cells to the therapeutic vector was determined after infection with ADV/RSV-tk with or without GCV. Subcutaneous tumors were established in syngeneic C3H/He female mice with 5 x 10(5) MBT-2 cells. Optimal dosing of ADV/RSV-tk was determined by direct percutaneous tumor injection with increasing viral doses and treatment with GCV. Treatment efficacy, long-term survival, and toxicity were determined in separate, similar, controlled experiments. RESULTS: In vitro studies indicated greater than 95% transduction 96 hours after inoculation at an MOI of 3000 and a greater than 95% cell death rate with RSV-tk + GCV at an MOI of 61 or greater. In vivo experiments demonstrated an optimal viral dose of 3 x 10(8) plaque-forming units (pfu) and a greater than fourfold reduction in tumor growth for the animals treated with ADV/RSV-tk compared with control animals (P = 0.0013). Toxicity was limited to histologic evidence of hepatitis with ADV/RSV-tk doses greater than 3 x 10(8) pfu + GCV. Long-term survival of treatment animals was significantly increased over that of control animals (59%, P = 0.0001). CONCLUSIONS: ADV/RSV-tk with GCV treatment results in efficient gene transfer in vitro and provides effective therapy in experimental murine bladder cancer by significantly inhibiting tumor growth and improving host survival.

Quinolinic acid lesion of the nigrostriatal pathway: effect on turning behaviour and protection by elevation of endogenous kynurenic acid in Rattus norvegicus.

Endogenous excitotoxins have been implicated in degeneration of nigral dopaminergic neurons in Parkinson's disease. It may be possible to reduce neurodegeneration by blocking the effects of these endogenous agents. The present study shows that contralateral turning seen following quinolinic acid-induced lesions of the nigrostriatal dopaminergic pathway was reversed by a treatment that increased brain levels of kynurenic acid, an endogenous excitatory amino acid antagonist. The treatment consisted of nicotinylalanine (5.6 nmol/5 microl i.c.v.), an inhibitor of kynureninase and kynurenine hydroxylase plus the precursor kynurenine (450 mg/kg i.p.) plus probenencid (200 mg/kg i.p.), an inhibitor of organic acid transport. Thus, neuroprotection by increasing brain kynurenic acid in vivo may be useful in retarding cell loss in Parkinson's and other neurodegenerative diseases involving excitotoxicity.

Adenovirus-mediated combination suicide and cytokine gene therapy for bladder cancer.

BACKGROUND: The present study tests the hypothesis that adenovirus-mediated transfer of murine IL-2 (ADV/RSV-mIL-2) alone or in combination with HSV-tk + GCV will improve antitumorigenic response in the murine MBT-2 model. MATERIALS AND METHODS: mIL-2 production and toxicity were determined in vitro using an ELISA and a cell proliferation assay. Tumor-bearing animals were randomly assigned into four treatment groups and directly injected with combinations of ADV/RSV-tk and ADV/RSV-mIL-2. In a separate experiment, the above-mentioned groups were followed by two subsequent treatments with ADV/RSV-mIL-2. RESULTS: Transduced MBT-2 cells were able to express mIL-2 in a time and dose dependent fashion. We could not demonstrate any improvement in antitumorigenic response with mIL-2 gene therapy alone or in combination with HSV-tk-suicide gene therapy over HSV-tk suicide gene therapy alone. CONCLUSIONS: Although ADV/RSV-mIL-2 transduced MBT-2 cells were able to produce large amounts of mIL-2 in vitro, we could not demonstrate significant tumor growth inhibition by adding mIL-2 gene therapy to suicide gene therapy. The growth inhibitory effects of sequential suicide and cytokine gene therapy were transient and not superior to single dose suicide and cytokine gene therapy.