Nitrogen deposition and its contribution to nitrogen cycling and associated soil processes

Human activity has greatly perturbed the nitrogen cycle through increased fixation by legumes, by energy and fertilizer production, and by the mobilization of N from long-term storage pools. This extra reactive N is readily transported through the environment, and there is increasing evidence that it is changing ecosystems through eutrophication and acidification. Rothamsted Experimental Station, UK has been involved in research on N cycling in ecosystems since its inception in 1843. Measurements of precipitation composition at Rothamsted, made since 1853, show an increase of nitrate and ammonium N in precipitation from 1 and 3 kg N ha(-1) yr(-1) respectively, in 1855 to a maximum of 8 and 10 kg N ha(-1) yr(-1) in 1980, decreasing to 4 and 5 kg N ha(-1) y(-1) today. Nitrogen inputs via dry deposition do, however, remain high. Recent measurements with diffusion tubes and filter packs show large concentrations of nitrogen dioxide of c. 20 mu g m(-3) in winter and c. 10 mu g m(-3) in summer; the difference is linked to the use of central heating, and with variations in wind direction and pollutant source. Concentrations of nitric acid and particulate N exhibit maxima of 1.5 and 2 mu g m(-3) in summer and winter, respectively. Concentrations of ammonia are small, barely rising above 1 mu g m(-3). Taking deposition velocities from the literature gives a total deposition of all measured N species to winter cereals of 43.3 kg N ha(-1) yr(-1), 84 % as oxidized species, 79 % dry deposited. The fate of this N deposited to the very long-term Broadbalk Continuous Wheat Experiment at Rothamsted has been simulated using the SUNDIAL N-cycling model: at equilibrium, after 154 yr of the experiment and with N deposition increasing from c. 10 kg ha(-1) yr(-1) in 1843 to 45 kg ha(-1) yr(-1) today, c. 5 % is leached, 12% is denitrified, 30% immobilized in the soil organic matter and 53 % taken off in the crop. The 'efficiency of use' of the deposited N decreases, and losses and immobilization increase as the amount of fertilizer N increases. The deposited N itself, and the acidification that is associated with it (from the nitric acid, ammonia and ammonium), has reduced the number of plant species on the 140-yr-old Park Grass hay meadow. It has also reduced methane oxidation rates in soil by c. 15 % under arable land and 30 % under woodland, and has caused N saturation of local woodland ecosystems: nitrous oxide emission rates of up to 1.4 kg ha(-1) yr(-1) are equivalent to those from arable land receiving > 200 kg N ha(-1) yr(-1), and in proportion to the excess N deposited; measurements of N cycling processes and pools using N-15 pool dilution techniques show a large nitrate pool and enhanced rates of nitrification relative to immobilization. Ratios of gross nitrification:gross immobilization might prove to be good indices of N saturation

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

Guillain-Barré syndrome: a century of progress

In 1916, Guillain, Barré and Strohl reported on two cases of acute flaccid paralysis with high cerebrospinal fluid protein levels and normal cell counts — novel findings that identified the disease we now know as Guillain–Barré syndrome (GBS). 100 years on, we have made great progress with the clinical and pathological characterization of GBS. Early clinicopathological and animal studies indicated that GBS was an immune-mediated demyelinating disorder, and that severe GBS could result in secondary axonal injury; the current treatments of plasma exchange and intravenous immunoglobulin, which were developed in the 1980s, are based on this premise. Subsequent work has, however, shown that primary axonal injury can be the underlying disease. The association of Campylobacter jejuni strains has led to confirmation that anti-ganglioside antibodies are pathogenic and that axonal GBS involves an antibody and complement-mediated disruption of nodes of Ranvier, neuromuscular junctions and other neuronal and glial membranes. Now, ongoing clinical trials of the complement inhibitor eculizumab are the first targeted immunotherapy in GBS

Current treatment practice of Guillain-Barré syndrome

Objective: To define the current treatment practice of Guillain-Barré syndrome (GBS). Methods: The study was based on prospective observational data from the first 1,300 patients included in the International GBS Outcome Study. We described the treatment practice of GBS in general, and for (1) severe forms (unable to walk independently), (2) no recovery after initial treatment, (3) treatment-related fluctuations, (4) mild forms (able to walk independently), and (5) variant forms including Miller Fisher syndrome, taking patient characteristics and hospital type into account. Results: We excluded 88 (7%) patients because of missing data, protocol violation, or alternative diagnosis. Patients from Bangladesh (n = 189, 15%) were described separately because 83% were not treated. IV immunoglobulin (IVIg), plasma exchange (PE), or other immunotherapy was provided in 941 (92%) of the remaining 1,023 patients, including patients with severe GBS (724/743, 97%), mild GBS (126/168, 75%), Miller Fisher syndrome (53/70, 76%), and other variants (33/40, 83%). Of 235 (32%) patients who did not improve after their initial treatment, 82 (35%) received a second immune modulatory treatment. A treatment-related fluctuation was observed in 53 (5%) of 1,023 patients, of whom 36 (68%) were re-treated with IVIg or PE. Conclusions: In current practice, patients with mild and variant forms of GBS, or with treatment-related fluctuations and treatment failures, are frequently treated, even in absence of trial data to support this choice. The variability in treatment practice can be explained in part by the lack of evidence and guidelines for effective treatment in these situations

The re-identification risk of Canadians from longitudinal demographics

<p>Abstract</p> <p>Background</p> <p>The public is less willing to allow their personal health information to be disclosed for research purposes if they do not trust researchers and how researchers manage their data. However, the public is more comfortable with their data being used for research if the risk of re-identification is low. There are few studies on the risk of re-identification of Canadians from their basic demographics, and no studies on their risk from their longitudinal data. Our objective was to estimate the risk of re-identification from the basic cross-sectional and longitudinal demographics of Canadians.</p> <p>Methods</p> <p>Uniqueness is a common measure of re-identification risk. Demographic data on a 25% random sample of the population of Montreal were analyzed to estimate population uniqueness on postal code, date of birth, and gender as well as their generalizations, for periods ranging from 1 year to 11 years.</p> <p>Results</p> <p>Almost 98% of the population was unique on full postal code, date of birth and gender: these three variables are effectively a unique identifier for Montrealers. Uniqueness increased for longitudinal data. Considerable generalization was required to reach acceptably low uniqueness levels, especially for longitudinal data. Detailed guidelines and disclosure policies on how to ensure that the re-identification risk is low are provided.</p> <p>Conclusions</p> <p>A large percentage of Montreal residents are unique on basic demographics. For non-longitudinal data sets, the three character postal code, gender, and month/year of birth represent sufficiently low re-identification risk. Data custodians need to generalize their demographic information further for longitudinal data sets.</p

Differential Differences in Methylation Status of Putative Imprinted Genes among Cloned Swine Genomes

DNA methylation is a major epigenetic modification in the mammalian genome that regulates crucial aspects of gene function. Mammalian cloning by somatic cell nuclear transfer (SCNT) often results in gestational or neonatal failure with only a small proportion of manipulated embryos producing live births. Many of the embryos that survive to term later succumb to a variety of abnormalities that are likely due to inappropriate epigenetic reprogramming. Aberrant methylation patterns of imprinted genes in cloned cattle and mice have been elucidated, but few reports have analyzed the cloned pig genome. Four surviving cloned sows that were created by ear fibroblast nuclear transfer, each with a different life span and multiple organ defects, such as heart defects and bone growth delay, were used as epigenetic study materials. First, we identified four putative differential methylation regions (DMR) of imprinted genes in the wild-type pig genome, including two maternally imprinted loci (INS and IGF2) and two paternally imprinted loci (H19 and IGF2R). Aberrant DNA methylation, either hypermethylation or hypomethylation, commonly appeared in H19 (45% of imprinted loci hypermethylated vs. 30% hypomethylated), IGF2 (40% vs. 0%), INS (50% vs. 5%), and IGF2R (15% vs. 45%) in multiple tissues from these four cloned sows compared with wild-type pigs. Our data suggest that aberrant epigenetic modifications occur frequently in the genome of cloned swine. Even with successful production of cloned swine that avoid prenatal or postnatal death, the perturbation of methylation in imprinted genes still exists, which may be one of reason for their adult pathologies and short life. Understanding the aberrant pattern of gene imprinting would permit improvements in future cloning techniques

Identification and relative quantification of tyrosine nitration in a model peptide using two-dimensional infrared spectroscopy

Nitration of tyrosine in proteins and peptides is a post-translational modification that occurs under conditions of oxidative stress. It is implicated in a variety of medical conditions, including neurodegenerative and cardiovascular diseases. However, monitoring tyrosine nitration and understanding its role in modifying biological function remains a major challenge. In this work, we investigate the use of electron-vibration-vibration (EVV) two-dimensional infrared (2DIR) spectroscopy for the study of tyrosine nitration in model peptides. We demonstrate the ability of EVV 2DIR spectroscopy to differentiate between the neutral and deprotonated states of 3-nitrotyrosine, and we characterize their spectral signatures using information obtained from quantum chemistry calculations and simulated EVV 2DIR spectra. To test the sensitivity of the technique, we use mixed-peptide samples containing various levels of tyrosine nitration, and we use mass spectrometry to independently verify the level of nitration. We conclude that EVV 2DIR spectroscopy is able to provide detailed spectroscopic information on peptide side-chain modifications and to detect nitration levels down to 1%. We further propose that lower nitration levels could be detected by introducing a resonant Raman probe step to increase the detection sensitivity of EVV 2DIR spectroscopy. (Graph Presented)

Comparative Genotyping of Campylobacter jejuni Strains from Patients with Guillain-Barré Syndrome in Bangladesh

Background: Campylobacter jejuni is a common cause of acute gastroenteritis and is associated with post-infectious neuropathies such as the Guillain-Barré syndrome (GBS) and the Miller Fisher syndrome (MFS). We here present comparative genotyping of 49 C. jejuni strains from Bangladesh that were recovered from patients with enteritis or GBS. All strains were serotyped and analyzed by lipo-oligosaccharide (LOS) genotyping, amplified fragment length polymorphism (AFLP) analysis, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Methodology/Principal Findings: C. jejuni HS:23 was a predominant serotype among GBS patients (50%), and no specific serotype was significantly associated with GBS compared to enteritis. PCR screening showed that 38/49 (78%) of strains could be assigned to LOS classes A, B, C, or E. The class A locus (4/7 vs 3/39; p<0.01) was significantly associated in the GBS-related strains as compared to enteritis strains. All GBS/oculomotor related strains contained the class B locus; which was also detected in 46% of control strains. Overlapping clonal groups were defined by MLST, AFLP and PFGE for strains from patients with gastroenteritis and GBS. MLST defined 22 sequence types (STs) and 7 clonal complexes including 7 STs not previously identified (ST-3742, ST-3741, ST-3743, ST-3748, ST-3968, ST-3969 and ST-3970). C. jejuni HS:23 strains from patients with GBS or enteritis were clonal and all strains belonged to ST-403 complex. Concordance between LOS class B and ST-403 complex was revealed. AFLP defined 25 different types at 90% similarity. The predominant AFLP type AF-20 coincided with the C. jejuni HS:23 and ST-403 complex. Conclusion/Significance: LOS genotyping, MLST, AFLP and PFGE helped to identify the HS:23 strains from GBS or enteritis patients as clonal. Overall, genotypes exclusive for enteritis or for GBS-related strains were not obtained although LOS class A was significantly associated with GBS str