Peroxiredoxin 6 represents a widely distributed group of peroxiredoxins that contain a single conserved cysteine in the protein monomer (1-cys Prdx). The cys when oxidized to the sulfenic form is ...reduced with glutathione (GSH) catalyzed by the π isoform of GSH-S-transferase. Three enzymatic activities of the protein have been described:1) peroxidase with H2O2, short chain hydroperoxides, and phospholipid hydroperoxides as substrates; 2) phospholipase A2 (PLA2); and 3) lysophosphatidylcholine acyl transferase (LPCAT). These activities have important physiological roles in antioxidant defense, turnover of cellular phospholipids, and the generation of superoxide anion via initiation of the signaling cascade for activation of NADPH oxidase (type 2). The ability of Prdx6 to reduce peroxidized cell membrane phospholipids (peroxidase activity) and also to replace the oxidized sn-2 fatty acyl group through hydrolysis/reacylation (PLA2 and LPCAT activities) provides a complete system for the repair of peroxidized cell membranes.
•Prdx6 expresses peroxidase, phospholipase A2, and lysophosphatidylcholine acyl transferase activities.•Reduction and resolution of oxidized Prdx6 is mediated by GSH catalyzed by GSH S-transferase π.•Prdx6 is a complete enzyme for the repair of peroxidized cell membranes.•Prdx6 participates in the synthesis and degradation of cellular phospholipids.•Prdx6 generates the lysophosphatidic acid that leads to activation of NADPH oxidase (type 2).
Peroxiredoxin 6 (Prdx6) is a Ca2+-independent intracellular phospholipase A2 (called aiPLA2) that is localized to cytosol, lysosomes, and lysosomal-related organelles. Activity is minimal at ...cytosolic pH but is increased significantly with enzyme phosphorylation, at acidic pH, and in the presence of oxidized phospholipid substrate; maximal activity with phosphorylated aiPLA2 is ∼2 µmol/min/mg protein. Prdx6 is a “moonlighting” protein that also expresses glutathione peroxidase and lysophosphatidylcholine acyl transferase activities. The catalytic site for aiPLA2 activity is an S32-H26-D140 triad; S32-H26 is also the phospholipid binding site. Activity is inhibited by a serine “protease” inhibitor (diethyl p-nitrophenyl phosphate), an analog of the PLA2 transition state 1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol (MJ33), and by two naturally occurring proteins (surfactant protein A and p67phox), but not by bromoenol lactone. aiPLA2 activity has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2 (NOX2). The enzyme has been implicated in acute lung injury, carcinogenesis, neurodegenerative diseases, diabetes, male infertility, and sundry other conditions, although its specific roles have not been well defined. Protein mutations and animal models are now available to further investigate the roles of Prdx6-aiPLA2 activity in normal and pathological physiology.
Significance Feedbacks from terrestrial ecosystems to atmospheric CO ₂ concentrations contribute the second-largest uncertainty to projections of future climate. These feedbacks, acting over huge ...regions and long periods of time, are extraordinarily difficult to observe and quantify directly. We evaluated in situ, atmospheric, and simulation estimates of the effect of CO ₂ on carbon storage, subject to mass balance constraints. Multiple lines of evidence suggest significant tropical uptake for CO ₂, approximately balancing net deforestation and confirming a substantial negative global feedback to atmospheric CO ₂ and climate. This reconciles two approaches that have previously produced contradictory results. We provide a consistent explanation of the impacts of CO ₂ on terrestrial carbon across the 12 orders of magnitude between plant stomata and the global carbon cycle.
Feedbacks from the terrestrial carbon cycle significantly affect future climate change. The CO ₂ concentration dependence of global terrestrial carbon storage is one of the largest and most uncertain feedbacks. Theory predicts the CO ₂ effect should have a tropical maximum, but a large terrestrial sink has been contradicted by analyses of atmospheric CO ₂ that do not show large tropical uptake. Our results, however, show significant tropical uptake and, combining tropical and extratropical fluxes, suggest that up to 60% of the present-day terrestrial sink is caused by increasing atmospheric CO ₂. This conclusion is consistent with a validated subset of atmospheric analyses, but uncertainty remains. Improved model diagnostics and new space-based observations can reduce the uncertainty of tropical and temperate zone carbon flux estimates. This analysis supports a significant feedback to future atmospheric CO ₂ concentrations from carbon uptake in terrestrial ecosystems caused by rising atmospheric CO ₂ concentrations. This feedback will have substantial tropical contributions, but the magnitude of future carbon uptake by tropical forests also depends on how they respond to climate change and requires their protection from deforestation.
Terrestrial ecosystems remove about 30 per cent of the carbon dioxide (CO2) emitted by human activities each year1, yet the persistence ofthis carbon sink depends partly on how plant biomass and soil ...organic carbon (SOC) stocks respond to future increases in atmospheric CO2 (refs. 23). Although plant biomass often increases in elevated CO2 (eCO2) experiments4-6, SOC has been observed to increase, remain unchanged or even decline7. The mechanisms that drive this variation across experiments remain poorly understood, creating uncertainty in climate projections8,9. Here we synthesized data from 108 eCO2 experiments and found that the effect of eCO2 on SOC stocks is best explained by a negative relationship with plant biomass: when plant biomass is strongly stimulated by eCO2, SOC storage declines; conversely, when biomass is weakly stimulated, SOC storage increases. This trade-off appears to be related to plant nutrient acquisition, in which plants increase their biomass by mining the soil for nutrients, which decreases SOC storage. We found that, overall, SOC stocks increase with eCO2 in grasslands (8 ± 2 per cent) but not in forests (0 ± 2 per cent), even though plant biomass in grasslands increase less (9 ± 3 per cent) than in forests (23 ± 2 per cent). Ecosystem models do not reproduce this trade-off, which implies that projections of SOC may need to be revised.
In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a ...useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens may be associated with increased CV risk factors in some patients with type 1 diabetes, and explore the complex relationships between weight gain, insulin resistance, glycaemic control and CV outcome. Important comparisons and contrasts between type 1 diabetes and type 2 diabetes are highlighted in terms of hepatic fat, fat partitioning and lipid profile, and how these may differ between type 1 diabetic patients with and without double diabetes. In so doing, we hope this work will stimulate much-needed research in this area and an improvement in clinical practice.
Numerous models of evapotranspiration have been published that range in data-driven complexity, but global estimates require a model that does not depend on intensive field measurements. The ...Priestley–Taylor model is relatively simple, and has proven to be remarkably accurate and theoretically robust for estimates of potential evapotranspiration. Building on recent advances in ecophysiological theory that allow detection of multiple stresses on plant function using biophysical remote sensing metrics, we developed a bio-meteorological approach for translating Priestley–Taylor estimates of potential evapotranspiration into rates of actual evapotranspiration. Five model inputs are required: net radiation (
R
n), normalized difference vegetation index (NDVI), soil adjusted vegetation index (SAVI), maximum air temperature (
T
max), and water vapor pressure (ea). Our model requires no calibration, tuning or spin-ups. The model is tested and validated against eddy covariance measurements (FLUXNET) from a wide range of climates and plant functional types—grassland, crop, and deciduous broadleaf, evergreen broadleaf, and evergreen needleleaf forests. The model-to-measurement
r
2 was 0.90 (RMS
=
16 mm/month or 28%) for all 16 FLUXNET sites across 2 years (most recent data release). Global estimates of evapotranspiration at a temporal resolution of monthly and a spatial resolution of 1° during the years 1986–1993 were determined using globally consistent datasets from the International Satellite Land-Surface Climatology Project, Initiative II (ISLSCP-II) and the Advanced Very High Resolution Spectroradiometer (AVHRR). Our model resulted in improved prediction of evapotranspiration across water-limited sites, and showed spatial and temporal differences in evapotranspiration globally, regionally and latitudinally.
Terrestrial ecosystems play a vital role in regulating the accumulation of carbon (C) in the atmosphere. Understanding the factors controlling land C uptake is critical for reducing uncertainties in ...projections of future climate. The relative importance of changing climate, rising atmospheric CO
, and other factors, however, remains unclear despite decades of research. Here, we use an ensemble of land models to show that models disagree on the primary driver of cumulative C uptake for 85% of vegetated land area. Disagreement is largest in model sensitivity to rising atmospheric CO
which shows almost twice the variability in cumulative land uptake since 1901 (1 s.d. of 212.8 PgC vs. 138.5 PgC, respectively). We find that variability in CO
and temperature sensitivity is attributable, in part, to their compensatory effects on C uptake, whereby comparable estimates of C uptake can arise by invoking different sensitivities to key environmental conditions. Conversely, divergent estimates of C uptake can occur despite being based on the same environmental sensitivities. Together, these findings imply an important limitation to the predictability of C cycling and climate under unprecedented environmental conditions. We suggest that the carbon modeling community prioritize a probabilistic multi-model approach to generate more robust C cycle projections.
Abstract
Water availability plays a critical role in shaping terrestrial ecosystems, particularly in low- and mid-latitude regions. The sensitivity of vegetation growth to precipitation strongly ...regulates global vegetation dynamics and their responses to drought, yet sensitivity changes in response to climate change remain poorly understood. Here we use long-term satellite observations combined with a dynamic statistical learning approach to examine changes in the sensitivity of vegetation greenness to precipitation over the past four decades. We observe a robust increase in precipitation sensitivity (0.624% yr
−1
) for drylands, and a decrease (−0.618% yr
−1
) for wet regions. Using model simulations, we show that the contrasting trends between dry and wet regions are caused by elevated atmospheric CO
2
(eCO
2
). eCO
2
universally decreases the precipitation sensitivity by reducing leaf-level transpiration, particularly in wet regions. However, in drylands, this leaf-level transpiration reduction is overridden at the canopy scale by a large proportional increase in leaf area. The increased sensitivity for global drylands implies a potential decrease in ecosystem stability and greater impacts of droughts in these vulnerable ecosystems under continued global change.
Phenylketonuria (PKU) is a genetic disease that is characterized by an inability to metabolize phenylalanine (Phe), which can result in neurotoxicity. To provide a potential alternative to a ...protein-restricted diet, we engineered Escherichia coli Nissle to express genes encoding Phe-metabolizing enzymes in response to anoxic conditions in the mammalian gut. Administration of our synthetic strain, SYNB1618, to the Pah
PKU mouse model reduced blood Phe concentration by 38% compared with the control, independent of dietary protein intake. In healthy Cynomolgus monkeys, we found that SYNB1618 inhibited increases in serum Phe after an oral Phe dietary challenge. In mice and primates, Phe was converted to trans-cinnamate by SYNB1618, quantitatively metabolized by the host to hippurate and excreted in the urine, acting as a predictive biomarker for strain activity. SYNB1618 was detectable in murine or primate feces after a single oral dose, permitting the evaluation of pharmacodynamic properties. Our results define a strategy for translation of live bacterial therapeutics to treat metabolic disorders.
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