Nutrient (C, N and P) enrichment induces significant changes in the soil metabolite profile and microbial carbon partitioning

The cycling of soil organic matter (SOM) and carbon (C) within the soil is governed by the presence of key macronutrients, particularly nitrogen (N) and phosphorus (P). The relative ratio of these nutrients has a direct effect on the potential rates of microbial growth and nutrient processing in soil and thus is fundamental to ecosystem functioning. However, the effect of changing soil nutrient stoichiometry on the small organic molecule (i.e., metabolite) composition and cycling by the microbial community remains poorly understood. Here, we aimed to disentangle the effect of stoichiometrically balanced nutrient addition on the soil metabolomic profile and apparent microbial carbon use efficiency (CUE) by adding a labile C source (glucose) in combination with N and/or P. After incorporation of the added glucose into the microbial biomass (48 h), metabolite profiling was undertaken by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). 494 metabolites were identified across all treatments mainly consisting of lipids (n = 199), amino acids (n = 118) and carbohydrates (n = 43), >97% of which showed significant changes in concentration between at least one treatment. Overall, glucose-C addition generally increased the synthesis of other carbohydrates in soil, while addition of C and N together increased peptide synthesis, indicative of protein formation and turnover. The combination of C and P significantly increased the number of fatty acids synthesised. There was no significant change in the PLFA-derived microbial community structure or microbial biomass following C, N and P addition. Further, N addition led to an increase in glucose-C partitioning into anabolic processes (i.e., increased CUE), suggesting the microbial community was N, but not P limited. Based on the metabolomic profiles observed here, we conclude that inorganic nutrient enrichment causes substantial shifts in both primary and secondary metabolism within the microbial community, leading to changes in resource flow and thus soil functioning, however, the microbial community illustrated significant metabolic flexibility

The role of alkalinity generation in controlling the fluxes of CO₂ during exposure and inundation on tidal flats

Dissolved inorganic carbon (DIC), gaseous CO2 and alkalinity fluxes from intertidal sediments were investigated during periods of exposure and inundation, using laboratory core incubations, previously published field data and reactive transport model simulations. In the incubations and previous field data, it was found that during periods of alkalinity production (attributed to the accumulation of reduced sulfur species within the sediment), the flux of DIC out of the sediment was greater during inundation than the gaseous CO2 flux during exposure by a factor of up to 1.8. This finding was supported by computational simulations which indicated that large amounts of sulfate reduction and reduced sulfur burial (FeS) induce an alkalinity flux from the sediment during high tide conditions. Model simulations also found that the amount of reactive Fe in the sediment was a major driver of net alkalinity production. Our finding that CO2 fluxes can be significantly lower than total metabolism during exposure has implications for how total metabolism is quantified on tidal flats

Chemical markers for rumen methanogens and methanogenesis

Peer reviewedPublisher PD

Benign recurrent intrahepatic cholestasis (BRIC): Evidence of genetic heterogeneity and delimitation of the BRIC locus to a 7-cM interval between D18S69 and D18S64

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disease characterized by multiple episodes of cholestasis without progression to chronic liver disease. The gene was previously assigned to chromosome 18q21, using a shared segment analysis in three families from the Netherlands. In the present study we report the linkage analysis of an expanded sample of 14 BRIC families, using 15 microsatellite markers from the 18q21 region. Obligate recombinants in two families place the gene in a 7-cM interval, between markers D18S69 and D18S64. All intervening markers had significant LOD scores in two-point linkage analysis. More over, we identified one family in which the BRIC gene seems to be unlinked to the 18q21 region, or that represents incomplete penetrance of the BRIC genotype

The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium.

BackgroundExcess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and findingsWe assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.ConclusionsThis study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer

Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers

__Background__ Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. __Methods__ We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and populationbased studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. __Findings__ We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·91%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73–2·89]