Essential Amino Acid-Enriched Diet Alleviates Dexamethasone-Induced Loss of Muscle Mass and Function through Stimulation of Myofibrillar Protein Synthesis and Improves Glucose Metabolism in Mice

Dexamethasone (DEX) induces dysregulation of protein turnover, leading to muscle atrophy and impairment of glucose metabolism. Positive protein balance, i.e., rate of protein synthesis exceeding rate of protein degradation, can be induced by dietary essential amino acids (EAAs). In this study, we investigated the roles of an EAA-enriched diet in the regulation of muscle proteostasis and its impact on glucose metabolism in the DEX-induced muscle atrophy model. Mice were fed normal chow or EAA-enriched chow and were given daily injections of DEX over 10 days. We determined muscle mass and functions using treadmill running and ladder climbing exercises, protein kinetics using the D2O labeling method, molecular signaling using immunoblot analysis, and glucose metabolism using a U-13C6 glucose tracer during oral glucose tolerance test (OGTT). The EAA-enriched diet increased muscle mass, strength, and myofibrillar protein synthesis rate, concurrent with improved glucose metabolism (i.e., reduced plasma insulin concentrations and increased insulin sensitivity) during the OGTT. The U-13C6 glucose tracing revealed that the EAA-enriched diet increased glucose uptake and subsequent glycolytic flux. In sum, our results demonstrate a vital role for the EAA-enriched diet in alleviating the DEX-induced muscle atrophy through stimulation of myofibrillar proteins synthesis, which was associated with improved glucose metabolism.

Formation and availability of methylmercury in mercury-contaminated sediment: effects of activated carbon and biochar amendments

Purpose As the formation of toxic and bioaccumulative methylmercury (MeHg) in Hg-contaminated sediments is of great concern worldwide, suitable remediation options are needed. Activated carbon (AC) amendment is a contested alternative due to uncertainties surrounding sorption efficiency and its potential role in aiding MeHg formation. The purpose of this study was therefore to demonstrate AC performance under favourable conditions for Hg-methylation and to further understand the role AC plays in the methylation process. Materials and methods Mercury-contaminated sediment (57.1 mg kg−1) was sampled from the Gunneklev fjord, a site known as the most heavily contaminated fjord in Norway. In a laboratory experiment, lignite AC (A-AC, 5%) or activated biochar (A-BC, 5%) along with dried algae biomass, serving as an excess source of easily degradable organic matter (OM) and sulphate, were added to sediment samples that were kept anoxic and dark over a period of 12 months. Results and discussion The amount of MeHg in sediment and porewater of the amended samples were measured at 0, 1, 3, 6, and 12 months and compared to an unamended control. A net increase of MeHg in the sediment was observed in both control and amended samples, but contrary to expectations, sediment MeHg was 5 and 3 times higher in the A-AC and A-BC treatments, respectively, relative to the control after 12 months. As the stimulation of Hg-methylation could not be attributed to the sorbents supplying more available OM or sulphate for dissimilatory sulphate reduction, it is speculated that the sorbents rather aid this process through shuttling of electrons between the substrates involved. Meanwhile, the A-AC and A-BC amendments strongly reduced the available MeHg-concentration in porewater (by 87% for A-AC and by 93% for A-BC after 12 months), confirming that AC sorbents can be used to effectively limit the transport of MeHg from sediments. Conclusion When considering remediation of OM-rich Hg-contaminated sediments with AC, caution is thus warranted, as the overall effect of reducing MeHg-transport out of the sediment could partly be offset by an increased fraction of MeHg in the sediment. Thin-layer capping with AC might therefore be preferable to complete mixing of AC and sediment.

The Development of a Technique for Sensitizing Cells of Various Origins for Biotechnological Purposes

The functional activity stimulation of cell cultures was tested in MDBK cell culture, photobacteria AliivibriofischeriandHalobacteriumhalobium. Theaim of the investigation was to increase the ”yield” of the cells using an environmentallysafe stimulant and membrane-tropic agent that isalso safe for the experimenter. Ultrasonicwaves were used.Experimental ultrasonic exposure varied within the following limits: time from 1 to 300 sec, SATA-intensity of 0.01–2.0 W/cm2, generation frequency of 0.88 or 2.64 MHz, standing or traveling wave. The modulation frequency range was within 0.1–150 Hz. The devices used were: UST-1-01F, UST-5 and UST1.02C. The modulating generators were G3–112 and CP–110.Stimulation of MDBK cell growth was initiated by US-intensity of 0.03–0.05 W/cm2 , with an exposure of 5–30 sec.Exposure to ultrasound with an intensity of 0.2–0.4 W/cm2 (for 3 min) had a stimulating effect on bioluminescence and was associated with an increase in the growth rate ofA. fischeri. The findings indicated that 0.4 W/cm2ultrasonic intensity and modulation frequencies from 0.25 to 0.7 Hz can stimulate the growth of archaea.It was revealed that the maximum proliferation index in all cases of stimulant application was noted in cultures with minimal initial proliferative activity in the control.The authors expect thatthese results on the possibilities of acoustic continuous and modulated waves can be applied for biotechnological purposes to develop a new biotechnological method. Keywords: cell culture, ultrasound, proliferation, stimulation

A Tear Metabolomic Profile Showing Increased Ornithine Decarboxylase Activity and Spermine Synthesis in Thyroid-Associated Orbitopathy

About half of patients with Graves’ disease develop an orbitopathy related to an inflammatory expansion of the periorbital adipose tissue and muscles. We used a targeted metabolomic approach measuring 188 metabolites by mass spectrometry to compare the metabolic composition of tears in patients with active (n = 21) versus inactive (n = 24) thyroid-associated orbitopathy. Among the 44 metabolites accurately measured, 8 showed a significant alteration of their concentrations between the two groups. Two short-chain acylcarnitines, propionylcarnitine and butyrylcarnitine, and spermine showed increased concentrations in the tears of patients with active orbitopathy, whereas ornithine, glycine, serine, citrulline and histidine showed decreased concentrations in this group. In addition, the ratio putrescine/ornithine, representing the activity of ornithine decarboxylase, was significantly increased in patients with active compared to inactive orbitopathy (p = 0.0011, fold change 3.75). The specificity of this candidate biomarker was maintained when compared to a control group with unclassified dry eye disease. Our results suggest that the stimulation of ornithine decarboxylase by TSH receptor autoantibodies in orbital fibroblasts could lead to increased synthesis of spermine, through the increased activity of ornithine decarboxylase, that may contribute to periorbital expansion in Graves’ ophthalmopathy.

IgA Complexes Induce Neutrophil Extracellular Trap Formation More Potently Than IgG Complexes

Neutrophil extracellular trap (NET) formation is a powerful instrument to fight pathogens, but may induce collateral damage in the affected tissues. Besides pathogen-derived factors, immune complexes are potent inducers of NET formation. Neutrophils express IgA and IgG specific Fc receptors (FcRs) and therefore respond to complexed IgA and IgG. Especially in the context of autoimmune diseases, IgA and IgG immune complexes have been shown to trigger NET formation, a process that putatively contributes to disease severity. However, it is of question if both antibody classes stimulate neutrophils to the same extent. In this study, we compared the capability of IgA and IgG complexes formed by heat aggregation to induce NET formation. While stimulation of neutrophils with IgA complexes robustly induced NET formation, complexed IgG only marginally increased the amount of NETs compared to the unstimulated control. Mixing IgA with IgG before heat aggregation did not increase the effect of complexed IgA on neutrophils. By contrast, the presence of IgG complexes seemed to disturb neutrophil stimulation by IgA complexes. The capacity of complexed IgG to induce NET formation could not be increased by the addition of autologous serum or the removal of terminal sialic acid in the Fc glycan. Together, our data show that IgA is a much more potent inducer of NET formation than IgG. IgA may thus be the main driving force in (auto)immune complex-mediated NET formation.

Lab-Scale Permeability Enhancement by Chemical Treatment in Fractured Granite (Cornubian Batholith) for the United Downs Deep Geothermal Power Project, Cornwall (UK)

A hydrothermal doublet system was drilled in a fault-related granitic reservoir in Cornwall. It targets the Porthtowan Fault Zone (PTF), which transects the Carnmenellis granite, one of the onshore plutons of the Cornubian Batholith in SW England. At 5058 m depth (TVD, 5275 m MD) up to 190 °C were reached in the dedicated production well. The injection well is aligned vertically above the production well and reaches a depth of 2393 m MD. As part of the design process for potential chemical stimulation of the open-hole sections of the hydrothermal doublet, lab-scale acidification experiments were performed on outcrop analogue samples from the Cornubian Batholith, which include mineralised veins. The experimental setup comprised autoclave experiments on sample powder and plugs, and core flooding tests on sample plugs to investigate to what degree the permeability of natural and artificial (saw-cut) fractures can be enhanced. All samples were petrologically and petrophysically analysed before and after the acidification experiments to track all changes resulting from the acidification. Based on the comparison of the mineralogical composition of the OAS samples with the drill cuttings from the production well, the results can be transferred to the hydrothermally altered zones around the faults and fractures of the PTF. Core Flooding Tests and Autoclave Experiments result in permeability enhancement factors of 4 to >20 and 0.1 to 40, respectively. Mineral reprecipitation can be avoided in the stimulated samples by sufficient post-flushing.