C4-dicarboxylates as growth substrates and signaling molecules for commensal and pathogenic enteric bacteria in mammalian intestine

The C4-dicarboxylates (C4-DC) L-aspartate and L-malate have been identified as playing an important role in the colonization of mammalian intestine by enteric bacteria, such as Escherichia coli and Salmonella Typhimurium, and succinate as a signaling molecule for host–enteric bacteria interaction. Thus, endogenous and exogenous fumarate respiration and related functions are required for efficient initial growth of the bacteria. L-aspartate represents a major substrate for fumarate respiration in the intestine and a high-quality substrate for nitrogen assimilation. During nitrogen assimilation, DcuA catalyzes an L-aspartate/fumarate antiport and serves as a nitrogen shuttle for the net uptake of ammonium only, whereas DcuB acts as a redox shuttle that catalyzes the L-malate/succinate antiport during fumarate respiration. The C4-DC two-component system DcuS-DcuR is active in the intestine and responds to intestinal C4-DC levels. Moreover, in macrophages and in mice, succinate is a signal that promotes virulence and survival of S . Tm and pathogenic E. coli . On the other hand, intestinal succinate is an important signaling molecule for the host and activates response and protective programs. Therefore, C4-DCs play a major role in supporting colonization of enteric bacteria and as signaling molecules for the adaptation of host physiology.

Trans-cerebral HCO3− and PCO2 exchange during acute respiratory acidosis and exercise-induced metabolic acidosis in humans

This study investigated trans-cerebral internal jugular venous-arterial bicarbonate ([HCO3−]) and carbon dioxide tension (PCO2) exchange utilizing two separate interventions to induce acidosis: 1) acute respiratory acidosis via elevations in arterial PCO2 (PaCO2) (n = 39); and 2) metabolic acidosis via incremental cycling exercise to exhaustion (n = 24). During respiratory acidosis, arterial [HCO3−] increased by 0.15 ± 0.05 mmol ⋅ l−1 per mmHg elevation in PaCO2 across a wide physiological range (35 to 60 mmHg PaCO2; P < 0.001). The narrowing of the venous-arterial [HCO3−] and PCO2 differences with respiratory acidosis were both related to the hypercapnia-induced elevations in cerebral blood flow (CBF) (both P < 0.001; subset n = 27); thus, trans-cerebral [HCO3−] exchange (CBF × venous-arterial [HCO3−] difference) was reduced indicating a shift from net release toward net uptake of [HCO3−] (P = 0.004). Arterial [HCO3−] was reduced by −0.48 ± 0.15 mmol ⋅ l−1 per nmol ⋅ l−1 increase in arterial [H+] with exercise-induced acidosis (P < 0.001). There was no relationship between the venous-arterial [HCO3−] difference and arterial [H+] with exercise-induced acidosis or CBF; therefore, trans-cerebral [HCO3−] exchange was unaltered throughout exercise when indexed against arterial [H+] or pH (P = 0.933 and P = 0.896, respectively). These results indicate that increases and decreases in systemic [HCO3−] – during acute respiratory/exercise-induced metabolic acidosis, respectively – differentially affect cerebrovascular acid-base balance (via trans-cerebral [HCO3−] exchange).

Airborne quantification of net methane and carbon dioxide fluxes from European Arctic wetlands in Summer 2019

Arctic wetlands and surrounding ecosystems are both a significant source of methane (CH 4 ) and a sink of carbon dioxide (CO 2 ) during summer months. However, precise quantification of this regional CH 4 source and CO 2 sink remains poorly characterized. A research flight using the UK Facility for Airborne Atmospheric Measurement was conducted in July 2019 over an area (approx. 78 000 km 2 ) of mixed peatland and forest in northern Sweden and Finland. Area-averaged fluxes of CH 4 and carbon dioxide were calculated using an aircraft mass balance approach. Net CH 4 fluxes normalized to wetland area ranged between 5.93 ± 1.87 mg m −2 h −1 and 4.44 ± 0.64 mg m −2 h −1 (largest to smallest) over the region with a meridional gradient across three discrete areas enclosed by the flight survey. From largest to smallest, net CO 2 sinks ranged between −513 ± 74 mg m −2 h −1 and −284 ± 89 mg m −2 h −1 and result from net uptake of CO 2 by vegetation and soils in the biosphere. A clear gradient of decreasing bulk and area-averaged CH 4 flux was identified from north to south across the study region, correlated with decreasing peat bog land area from north to south identified from CORINE land cover classifications. While N 2 O mole fraction was measured, no discernible gradient was measured over the flight track, but a minimum flux threshold using this mass balance method was calculated. Bulk (total area) CH 4 fluxes determined via mass balance were compared with area-weighted upscaled chamber fluxes from the same study area and were found to agree well within measurement uncertainty. The mass balance CH 4 fluxes were found to be significantly higher than the CH 4 fluxes reported by many land-surface process models compiled as part of the Global Carbon Project. There was high variability in both flux distribution and magnitude between the individual models. This further supports previous studies that suggest that land-surface models are currently ill-equipped to accurately capture carbon fluxes inthe region. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 2)'.

Receptor depletion and recovery in small-intestinal neuroendocrine tumors and normal tissues after administration of a single intravenous dose of octreotide measured by 68Ga-DOTATOC PET/CT

Background Low-grade neuroendocrine tumors (NETs) are characterized by an abundance of somatostatin receptors (SSTR) that can be targeted with somatostatin analogs (SSA). When activated with a single dose of SSA, the receptor-ligand complex is internalized, and the receptor is by default recycled within 24 h. Ongoing medication with long-acting SSAs at 68Ga-DOTA-SSA-PET has been shown to increase the tumor-to-normal organ contrast. This study was performed to investigate the time-dependent extended effect (7 h) of a single intravenous dose of 400 µg short-acting octreotide on the tumor versus normal tissue uptake of 68Ga-DOTATOC. Methods Patients with small-intestinal NETs received a single intravenous dose of 400 µg octreotide and underwent dynamic abdominal 68Ga-DOTATOC-PET/CT at three sessions (0, 3 and 6 h) plus static whole-body (WB) PET/CT (1, 4 and 7 h), starting each PET/CT session by administering 167 ± 21 MBq, 23.5 ± 4.2 µg (mean ± SD, n = 12) of 68Ga-DOTATOC. A previously acquired clinical whole-body 68Ga-DOTATOC scan was used as baseline. SUV and net uptake rate Ki were calculated in tumors, and SUV in healthy organs. Results Tumor SUV decreased significantly from baseline to 1 h post-injection but subsequently increased over time and became similar to baseline at 4 h and 7 h. The tumor net uptake rate, Ki, similarly increased significantly over time and showed a linear correlation both with SUV and tumor-to-blood ratio. By contrast, the uptake in liver, spleen and pancreas remained significantly below baseline levels also at 7 h and the receptor turn-over in tumors thus exceeded that in the normal tissue, with restitution of tumor 68Ga-DOTATOC uptake mainly completed at 7 h. These results however differed depending on tumor size, with significant increases in Ki and SUV between the 1st and 2nd PET, in large tumors (≥ 4 mL) but not in small (> 1 to < 4 mL) tumors. Conclusion SSTR recycling is faster in small-intestinal NETs than in liver, spleen and pancreas. This opens the possibility to protect normal tissues during PRRT by administering a single dose of cold peptide hours before peptide receptor radionuclide therapy (PRRT), and most likely additionally improve the availability and uptake of the therapeutic preparation in the tumors.

Resolvin T-series Reduce Neutrophil Extracellular Traps

The newly identified thirteen-series Resolvins (RvTs) regulate phagocyte functions and accelerate resolution of infectious inflammation. Since SARS-CoV-2 elicits uncontrolled inflammation involving neutrophil extracellular traps (NETs), we tested whether stereochemically defined RvTs regulate NET formation. Using microfluidic devices capturing NETs in PMA-stimulated human whole blood, the RvTs, RvT1-RvT4, 2.5 nM each, potently reduced NETs. With IL-1b-stimulated human neutrophils, each RvT dose- and time-dependently decreased NETosis giving ~50% potencies at 10 nM, compared to the known NETosis inhibitors [10 mM]. In mouse Staphylococcus aureus infection, RvTs [50 ng each] limited neutrophil infiltration, bacterial titers and NETs. Additionally, each RvT enhanced NET uptake by human macrophages; RvT2 was the most potent of the four RvTs, giving &gt;50% increase in NET-phagocytosis. As part of the intracellular signaling mechanism, RvT2 increased cAMP and phospho-AMPK within human macrophages, and RvT2-stimulated NET uptake was abolished by PKA and AMPK inhibition. RvT2 also stimulated NET clearance by mouse macrophages in vivo. Together, these results provide evidence for novel pro-resolving functions of RvTs, namely reducing NETosis and enhancing macrophage NET clearance via a cAMP-PKA-AMPK axis. Thus, RvTs open opportunities for regulating NET-mediated collateral tissue damage during infection as well as monitoring NETs.

Differential Physiological Responses to Salt Stress between Salt-Sensitive and Salt-Tolerant japonica Rice Cultivars at the Post-Germination and Seedling Stages

Soil salinity is a key source of abiotic stress in the cultivation of rice. In this study, two currently cultivated japonica rice species—Zhegeng 78 (salt-tolerant) and Zhegeng 99 (salt-sensitive)—with similar backgrounds were identified and used to investigate their differential responses to salt stress at the post-germination and seedling stages. Quantitative RT-PCR analysis demonstrated that the expression of OsSOS1, OsHAK1, and OsHAK5 at the post-germination stage, and the expression of OsHKT1,1, OsHTK2,1, and OsHAK1 at the seedling stage, were significantly higher in the salt-tolerant Zhegeng 78 compared with those of the salt-sensitive Zhegeng 99 under salt stress. The significantly lower Na+ net uptake rate at the post-germination and higher K+ net uptake rates at the post-germination and seedling stages were observed in the salt-tolerant Zhegeng 78 compared with those of the salt-sensitive Zhegeng 99 under salt stress. Significantly higher activity of peroxidase (POD) and the lower hydrogen peroxide (H2O2) accumulation were observed in the salt-tolerant Zhegeng 78 compared with those of salt-sensitive Zhegeng 99 under salt stress at the seeding stage. The salt-tolerant Zhegeng 78 might be valuable in future cultivation in salinity soils.

Distinct Roles of N-Terminal Fatty Acid Acylation of the Salinity-Sensor Protein SOS3

The Salt-Overly-Sensitive (SOS) pathway controls the net uptake of sodium by roots and the xylematic transfer to shoots in vascular plants. SOS3/CBL4 is a core component of the SOS pathway that senses calcium signaling of salinity stress to activate and recruit the protein kinase SOS2/CIPK24 to the plasma membrane to trigger sodium efflux by the Na/H exchanger SOS1/NHX7. However, despite the well-established function of SOS3 at the plasma membrane, SOS3 displays a nucleo-cytoplasmic distribution whose physiological meaning is not understood. Here, we show that the N-terminal part of SOS3 encodes structural information for dual acylation with myristic and palmitic fatty acids, each of which commands a different location and function of SOS3. N-myristoylation at glycine-2 is essential for plasma membrane association and recruiting SOS2 to activate SOS1, whereas S-acylation at cysteine-3 redirects SOS3 toward the nucleus. Moreover, a poly-lysine track in positions 7–11 that is unique to SOS3 among other Arabidopsis CBLs appears to be essential for the correct positioning of the SOS2-SOS3 complex at the plasma membrane for the activation of SOS1. The nuclear-localized SOS3 protein had limited bearing on the salt tolerance of Arabidopsis. These results are evidence of a novel S-acylation dependent nuclear trafficking mechanism that contrasts with alternative subcellular targeting of other CBLs by S-acylation.

Long-term fluxes of carbonyl sulfide and their seasonality and interannual variability in a boreal forest

The seasonality and interannual variability of terrestrial carbonyl sulfide (COS) flux are poorly constrained. We present the first easy-to-use parameterization for net COS forest sink based on the longest eddy covariance record from a boreal pine forest, covering 32 months over 5 years. Fluxes from hourly to yearly scales are reported, with the aim of revealing controlling factors and the level of interannual variability. The parameterization is based on the photosynthetically active radiation, vapor pressure deficit, air temperature, and leaf area index. The spring recovery of the flux after the winter dormancy period was mostly governed by air temperature, and the onset of the uptake varied by 2 weeks. For the first time, we report a significant reduction of ecosystem-scale COS flux under large water vapor pressure deficit in summer. The maximum monthly and weekly median COS uptake varied 26 and 20 % between years, respectively. The timing of the latter varied by 6 weeks. The fraction of the nocturnal uptake remained below 21 % of the total COS uptake. We observed the growing season (April–August) average net uptake of COS totaling −58.0 gS ha−1 with 37 % interannual variability. The long-term flux observations were scaled up to evergreen needleleaf forests (ENFs) in the whole boreal region by the Simple Biosphere Model Version 4 (SiB4). The observations were reparameterized by using SiB4 meteorological drivers and phenology. The total COS uptake by boreal ENF was in line with a missing COS sink at high latitudes pointed out in earlier studies.

Molecular-dynamics-simulation-guided membrane engineering allows the increase of membrane fatty acid chain length in Saccharomyces cerevisiae

The use of lignocellulosic-based fermentation media will be a necessary part of the transition to a circular bio-economy. These media contain many inhibitors to microbial growth, including acetic acid. Under industrially relevant conditions, acetic acid enters the cell predominantly through passive diffusion across the plasma membrane. The lipid composition of the membrane determines the rate of uptake of acetic acid, and thicker, more rigid membranes impede passive diffusion. We hypothesized that the elongation of glycerophospholipid fatty acids would lead to thicker and more rigid membranes, reducing the influx of acetic acid. Molecular dynamics simulations were used to predict the changes in membrane properties. Heterologous expression of Arabidopsis thaliana genes fatty acid elongase 1 (FAE1) and glycerol-3-phosphate acyltransferase 5 (GPAT5) increased the average fatty acid chain length. However, this did not lead to a reduction in the net uptake rate of acetic acid. Despite successful strain engineering, the net uptake rate of acetic acid did not decrease. We suggest that changes in the relative abundance of certain membrane lipid headgroups could mitigate the effect of longer fatty acid chains, resulting in a higher net uptake rate of acetic acid.

Forest biomass accumulation is an important source of acidity to forest soils: Data from Swedish inventories of forests and soils 1955 to 2010

The input of acidity to Swedish forest soils through forestry between 1955 and 2010 is compared with the acid input from atmospheric deposition. Depending on region, input of acidity from forestry was the minor part (25–45%) of the study period’s accumulated acid input but is now the dominating source (140–270 molc ha−1 year−1). The net uptake of cations due to the increase in standing forest biomass, ranged between 35 and 45% of the forestry related input of acidity while whole-tree harvesting, introduced in the late 1990s, contributed only marginally (< 2%). The geographical gradient in acid input is reflected in the proportion of acidified soils in Sweden but edaphic properties contribute to variations in acidification sensitivity. It is important to consider the acid input due to increases in standing forest biomass in acidification assessments since it is long-term and quantitatively important.