Abstract only
In patients with chronic autonomic failure (AF), drinking water increases mean blood pressure (MBP). This is an “osmopressor” response mediated by osmoreceptors on afferent neurons with ...their cell bodies in the dorsal root ganglia (DRG). Osmoreceptor activation triggers sympathetic excitation via a spinal reflex. Familial dysautonomia (FD) is a genetic disease that affects the development of primary afferent neurons with cell bodies in the DRG, but leaves efferent sympathetic neurons functionally intact. Our objective was to investigate whether this osmopressor response was present in FD. Beat‐to‐beat BP and RR intervals were recorded for 10 minutes prior and for 30 minutes after ingesting 500ml of water while supine. Thirty minutes after the water, MBP was significantly higher in the patients with AF than in those with FD (Δ15±5mmHg and Δ0±4mmHg respectively, P<0.01). Area under the curve also differed significantly between groups (191±25 and 387±55 mmHg/min, P<0.004). Blunting of the osmopressor response to water in patients with FD suggests that the congenital mutation affects osmosensory neurons.
Metabolomics is the quantification of small molecules, commonly known as metabolites. Collectively, these metabolites and their interactions within a biological system are known as the metabolome. ...The metabolome is a unique area of study, capturing influences from both genotype and environment. The availability of high-throughput technologies for quantifying large numbers of metabolites, as well as lipids and lipoprotein particles, has enabled detailed investigation of human metabolism in large-scale epidemiological studies. The Born in Bradford (BiB) cohort includes 12,453 women who experienced 13,776 pregnancies recruited between 2007-2011, their partners and their offspring. In this data note, we describe the metabolomic data available in BiB, profiled during pregnancy, in cord blood and during early life in the offspring. These include two platforms of metabolomic profiling: nuclear magnetic resonance and mass spectrometry. The maternal measures, taken at 26-28 weeks' gestation, can provide insight into the metabolome during pregnancy and how it relates to maternal and offspring health. The offspring cord blood measurements provide information on the fetal metabolome. These measures, alongside maternal pregnancy measures, can be used to explore how they may influence outcomes. The infant measures (taken around ages 12 and 24 months) provide a snapshot of the early life metabolome during a key phase of nutrition, environmental exposures, growth, and development. These metabolomic data can be examined alongside the BiB cohorts' extensive phenotype data from questionnaires, medical, educational and social record linkage, and other 'omics data.
Proteomics is the identification, detection and quantification of proteins within a biological sample. The complete set of proteins expressed by an organism is known as the proteome. The availability ...of new high-throughput proteomic technologies, such as Olink Proteomic Proximity Extension Assay (PEA) technology has enabled detailed investigation of the circulating proteome in large-scale epidemiological studies. In particular, the Olink® Target 96 inflammatory panel allows the measurement of 92 circulating inflammatory proteins. The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1991-1992 and has followed these women, their partners, and their offspring ever since. In this data note, we describe the proteomic data available in ALSPAC. Ninety-two proteins were analysed in 9000 blood plasma samples using the Olink® Target 96 inflammatory panel. Samples were derived from 2968 fasted mothers (mean age 47.5; Focus on Mothers 1 (FOM1)), 3005 non-fasted offspring at age 9 (Focus@9) and 3027 fasted offspring at age 24 (Focus@24). Post sample filtering, 1834 offspring have data at both timepoints and 1119 of those have data from their mother available. We performed quality control analyses using a standardised data processing workflow (
metaboprep
) to produce a filtered dataset of 8983 samples for researchers to use in future analyses. Initial validation analyses indicate that IL-6 measured using the Olink® Target 96 inflammatory panel is highly correlated with IL-6 previously measured by clinical chemistry (Pearson’s correlation = 0.77) and we are able to reproduce the reported positive correlation between body mass index (BMI) and IL-6. The pre-processing and validation analyses indicate a rich proteomic dataset to further characterise the role of inflammation in health and disease.
Carboxyl methyltransferase (CMT) enzymes catalyse the biomethylation of carboxylic acids under aqueous conditions and have potential for use in synthetic enzyme cascades. Herein we report that the ...enzyme FtpM from Aspergillus fumigatus can methylate a broad range of aromatic mono‐ and dicarboxylic acids in good to excellent conversions. The enzyme shows high regioselectivity on its natural substrate fumaryl‐l‐tyrosine, trans, trans‐muconic acid and a number of the dicarboxylic acids tested. Dicarboxylic acids are generally better substrates than monocarboxylic acids, although some substituents are able to compensate for the absence of a second acid group. For dicarboxylic acids, the second methylation shows strong pH dependency with an optimum at pH 5.5–6. Potential for application in industrial biotechnology was demonstrated in a cascade for the production of a bioplastics precursor (FDME) from bioderived 5‐hydroxymethylfurfural (HMF).
The carboxyl methyltransferase FtpM can catalyse methylation and dimethylation of a wide range of mono‐ and dicarboxylic acids, showing high regioselectivity for some diacids. The enzymatic methylation works under aqueous conditions and can therefore be integrated into enzyme cascades as demonstrated by the two‐step, one‐pot conversion of bioderived HMF to bioplastics precursor FDME.
Contact‐dependent growth inhibition (CDI) is an important mechanism of intercellular competition between neighboring Gram‐negative bacteria. CDI systems encode large surface‐exposed CdiA effector ...proteins that carry a variety of C‐terminal toxin domains (CdiA‐CTs). All CDI+ bacteria also produce CdiI immunity proteins that specifically bind to the cognate CdiA‐CT and neutralize its toxin activity to prevent auto‐inhibition. Here, the X‐ray crystal structure of a CdiI immunity protein from Neisseria meningitidis MC58 is presented at 1.45 Å resolution. The CdiI protein has structural homology to the Whirly family of RNA‐binding proteins, but appears to lack the characteristic nucleic acid‐binding motif of this family. Sequence homology suggests that the cognate CdiA‐CT is related to the eukaryotic EndoU family of RNA‐processing enzymes. A homology model is presented of the CdiA‐CT based on the structure of the XendoU nuclease from Xenopus laevis. Molecular‐docking simulations predict that the CdiA‐CT toxin active site is occluded upon binding to the CdiI immunity protein. Together, these observations suggest that the immunity protein neutralizes toxin activity by preventing access to RNA substrates.
The present study determined the influence of initial moisture conditions on the production and consumption of nitrous oxide (N sub(2)O) during denitrification and on the isotopic fingerprint of ...soil-emitted N sub(2)O. Sieved arable soil was pre-incubated at two different moisture contents: pre-wet at 75% and pre-dry at 20% water-filled pore space. After wetting to 90% water-filled pore space the soils were amended with glucose (400 kg C ha super(-1)) and KNO sub(3) (80 kg N ha super(-1)) and incubated for 10 days under a He/O sub(2)-atmosphere. Antecedent moisture conditions affected denitrification. N sub(2) + N sub(2)O fluxes and the N sub(2)O-to-N sub(2) ratio were higher in soils which were pre-incubated under dry conditions, probably because mobilization of organic C during the pre-treatment enhanced denitrification. Gaseous N fluxes showed similar time patterns of production and reduction of N sub(2)O in both treatments, where N sub(2)O fluxes were initially increasing and maximised 3-4 days after fertilizer application, and N sub(2) fluxes were delayed by 1-2 days. Time courses of delta super(15)N super(bulk)-N sub(2)O and delta super(18)O-N sub(2)O exhibited in both treatments increasing trends until maximum N sub(2) fluxes occurred, reflecting isotope fractionation during intense NO sub(3) super(-) reduction. Later this trend slowed down in the pre-dry treatment, while delta super(18)O-N sub(2)O was constant and delta super(15)N super(bulk)-N sub(2)O decreased in the pre-wet treatment. We explain these time patterns by non-homogenous distribution of NO sub(3) super(-) and denitrification activity, resulting from application of NO sub(3) super(-) and glucose to the surface of the soil. We assume that several process zones were thus created, which affected differently the isotopic signature of N sub(2)O and the N sub(2)O and N sub(2) fluxes during the different stages of the process. We modelled the delta super(15)N super(bulk)-N sub(2)O using process rates and associated fractionation factors for the pre-treated soils, which confirmed our hypothesis. The site preference (SP) initially decreased while N sub(2)O reduction was absent, which we could not explain by the N-flux pattern. During the subsequent increase in N sub(2) flux, SP and delta super(18)O-N sub(2)O increased concurrently, confirming that this isotope pattern is indicative for N sub(2)O reduction to N sub(2). The possible effect of the antecedent moisture conditions of the soil on N sub(2)O emissions was shown to be important.
A two-day Discussion Meeting of the Royal Society, ‘The Nitrogen
Cycle’, held in London in June
1991 (Stewart & Rosswall, 1992) reviewed the considerable progress
made in understanding the N cycle
in ...agricultural, forest and aquatic systems. The meeting included
some discussion of the concerns which
were already being expressed at that time over nitrate in water
supplies, and the impacts of nitrogenous
gases on tropospheric chemistry, the greenhouse effect and the
ozone layer. Since then, disquiet over the
impacts of nitrogenous compounds on the environment has increased, and
numerous papers have been
published on many aspects of the problem. We now have much
better understanding of the size and
scale of the perturbation of the N cycle, and several review papers
have highlighted the complexity of
the formidable issues that are challenging environmental scientists
(Vitousek, 1994; Galloway et al., 1995; Vitousek et al.,
1997).
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