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.

In-situ quantification of NO synthesis in a warm air glow discharge by WMS-based Mid-IR QCL absorption spectroscopy

Nitric oxide (NO) is one of the most crucial products in the plasma-based nitrogen fixation process. In this work, in-situ measurements were performed for quantifying the NO synthesis spatially in a warm air glow discharge, through the method of Mid-infrared quantum cascade laser absorption spectroscopy (QCL-AS). Two ro-vibrational transitions at 1900.076 cm-1 and 1900.517 cm-1 of the ground-state NO(X) were probed sensitively by the help of the wavelength modulation spectroscopy (WMS) approach to increase the signal/noise (S/N) level. The results show a decline trend of NO synthesis rate along the discharge channel from the cathode to the anode. However, from the point of energy efficiency, the cathode region is of significantly low energy efficiency of NO production. Severe disproportionality was found for the high energy consumption but low NO production in the region of cathode area, compared to that in the positive column zone. Further analysis demonstrates the high energy cost of NO production in the cathode region, is ascribed to the extremely high reduced electric field E/N therein not selectively preferable for the processes of vibrational excitation or dissociation of N2 and O2 molecules. This drags down the overall energy efficiency of NO synthesis by this typical warm air glow discharge, particularly for the ones with short electrode gaps. Limitations of further improving the energy cost of NO synthesis by variations of the discharge operation conditions, such as discharge current or airflow rate, imply other effective manners able to tune the energy delivery selectively to the NO formation process, are sorely needed.

Insight Into the Anti-staphylococcal Activity of JBC 1847 at Sub-Inhibitory Concentration

Multidrug-resistant pathogens constitute a serious global issue and, therefore, novel antimicrobials with new modes of action are urgently needed. Here, we investigated the effect of a phenothiazine derivative (JBC 1847) with high antimicrobial activity on Staphylococcus aureus, using a wide range of in vitro assays, flow cytometry, and RNA transcriptomics. The flow cytometry results showed that JBC 1847 rapidly caused depolarization of the cell membrane, while the macromolecule synthesis inhibition assay showed that the synthesis rates of DNA, RNA, cell wall, and proteins, respectively, were strongly decreased. Transcriptome analysis of S. aureus exposed to sub-inhibitory concentrations of JBC 1847 identified a total of 78 downregulated genes, whereas not a single gene was found to be significantly upregulated. Most importantly, there was downregulation of genes involved in adenosintrifosfat (ATP)-dependent pathways, including histidine biosynthesis, which is likely to correlate with the observed lower level of intracellular ATP in JBC 1847–treated cells. Furthermore, we showed that JBC 1847 is bactericidal against both exponentially growing cells and cells in a stationary growth phase. In conclusion, our results showed that the antimicrobial properties of JBC 1847 were primarily caused by depolarization of the cell membrane resulting in dissipation of the proton motive force (PMF), whereby many essential bacterial processes are affected. JBC 1847 resulted in lowered intracellular levels of ATP followed by decreased macromolecule synthesis rate and downregulation of genes essential for the amino acid metabolism in S. aureus. Bacterial compensatory mechanisms for this proposed multi-target activity of JBC 1847 seem to be limited based on the observed very low frequency of resistance toward the compound.

Polymorphism detection of <i>DGAT1</i> and <i>Lep</i> genes in Anatolian water buffalo (<i>Bubalus bubalis</i>) populations in Turkey

Acyl-CoA: diacylglycerol–acyltransferase 1 (DGAT1) enzyme plays a key role in controlling the synthesis rate triglyceride from diacylglycerol. Leptin (LP, OB, obese) is an important hormone that synthesizes mostly from adipose tissue and regulates glucose metabolism and homeostasis. DGAT1 and Lep genes are closely related to reproduction, growth, milk yield and composition in water buffalo breeds. This study aimed to identify genetic variation in the DGAT1 and Lep gene regions in 150 water buffalo individuals from five different provinces of Turkey using DNA sequencing. A total of 38 nucleotide variations and indels have identified 761 bp long partial intron 2 and exon 3 and 5′ UTR regions of the Lep gene in Anatolian water buffalo populations; 422 bp long partial exon 7–9 and exon 8 regions of DGAT1 gene were amplified and two mutations were defined in the point of 155 and 275 nucleotide that is three genotypes for S allele and Y allele of DGAT1 gene in intron 7 in Anatolian buffalo populations, respectively. These SNPs may have an effect on reproduction, growth, milk yield and composition in water buffalo populations and may prove to be useful for water buffalo breeding.

The Correlation Among the Immunoglobulin G Synthesis Rate, IgG Index and Albumin Quotient in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Retrospective Case–Control Study

Background: The immunoglobulin G synthesis rate (IgG SR) and immunoglobulin G (IgG) index are indicators of abnormal intrathecal humoural immune responses, and the albumin quotient (QALB) is an indicator used to evaluate the completeness of the blood-cerebrospinal fluid barrier (BCB). No systematic reports regarding differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are available. We assessed differences in the IgG SR, IgG index and QALB between GBS and CIDP patients in a Chinese cohort.Methods: A total of 234 patients were retrospectively enrolled in this study, and 167 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 67 non-GBS and non-CIDP patients requiring cerebrospinal fluid (CSF) examination were enrolled as the control group. The IgG SR, IgG index and QALB were calculated using formulas. The relevant clinical data were subjected to statistical analysis.Results: Among the GBS and CIDP study groups and the control group, the QALB had the highest positive rate (80.00%) in the CIDP group (P &lt; 0.01). The QALB stratification analysis showed that the ranges of 10 &lt; QALB ≤ 30 were dominant in the GBS and CIDP groups, and the positive rate of CIDP was higher than that of GBS. Furthermore, a QALB ≤ 7 was dominant in the control group, and a QALB &gt; 30 was dominant in the CIDP group. In receiver operating characteristic (ROC) curve analysis with the CIDP group as the trial group and the GBS group as the control group, the differences in the QALB were statistically significant (P &lt; 0.01). To achieve a high specificity of 98~99%, the diagnostic cut-off value for the QALB was above 57.37 (sensitivity: 9.33%) or below 0.60 (sensitivity: 4.35%). Multivariate logistic regression analysis showed that the CIDP patients had a QALB higher than 57.37, and compared with that in the GBS patients, the difference in the QALB was statistically significant (P &lt; 0.01).Conclusion: QALB elevation was associated with CIDP, while QALB values above 57.37 or below 0.60 had high specificity in differentiating between GBS and CIDP. In CIDP, the BCB is generally moderately to severely damaged; in GBS, the BCB is generally moderately damaged.

Transformation Rule-Based Molecular Evolution for Automatic Gasoline Molecule Design

Automatic molecular design on computers is an emerging technology for the determination of optimal fuel molecules. We developed a computer-aided molecular design framework through a transformation rule-based molecular evolution method. The reaction rule was used as the elementary step to change the molecular structure. A molecule can achieve structural variation continuously using a series of reaction rules. The finding of the optimal molecule can be seen as the evolution of structure in the chemical space, which was guided by using a global optimization algorithm to select the best reaction routine. We showed that the optimized molecule is independent of the input initial structure, proving the robustness of the method. We then applied the method to design gasoline molecules for motor and aviation gasoline. The designed molecules can not only serve as competitive candidate components for high-quality gasoline, but also accelerate the synthesis rate of new molecules in the laboratory.

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

The organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold attachment factor A (SAF-A), also known as Heteronuclear Ribonucleoprotein Protein U (HNRNPU), contributes to the formation of open chromatin structure. Here we demonstrate that SAF-A promotes the normal progression of DNA replication, and enables resumption of replication after inhibition. We report that cells depleted for SAF-A show reduced origin licensing in G1 phase, and consequently reduced origin activation frequency in S phase. Replication forks also progress less consistently in cells depleted for SAF-A, contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed two distinct effects of SAF-A depletion: first, the boundaries between early- and late-replicating domains become more blurred; and second, SAF-A depletion causes replication timing changes that tend to bring regions of discordant domain compartmentalisation and replication timing into concordance. Associated with these defects, SAF-A-depleted cells show elevated -H2AX formation and tend to enter quiescence. Overall we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.

Co/Ba/La2O3 catalyst for ammonia synthesis under mild reaction conditions

Ruthenium catalysts may allow realization of renewable energy–based ammonia synthesis processes using mild reaction conditions (<400 °C, <10 MPa). However, ruthenium is relatively rare and therefore expensive. Here, we report a Co nanoparticle catalyst loaded on a basic Ba/La2O3 support and pre-reduced at 700 °C (Co/Ba/La2O3_700red) that showed higher ammonia synthesis activity at 350 °C and 1.0–3.0 MPa than two benchmark Ru catalysts, Cs+/Ru/MgO and Ru/CeO2. The synthesis rate of the catalyst at 350 °C and 1.0 MPa (19.3 mmol h−1g−1) was 8.0 times that of Co/Ba/La2O3_500red and 6.9 times that of Co/La2O3_700red. The catalyst showed activity at temperatures down to 200 °C. High-temperature reduction induced formation of a BaO-La2O3 nano-fraction around the Co nanoparticles, which increased turnover frequency, inhibited Co nanoparticle sintering, and suppressed ammonia poisoning. These strategies may also be appliable to nickel catalysts.

Influence of B2O3 doping on synthesis of MgTiO3 ceramics from recycled magnesia-hercynite materials

Herein, magnesium metatitanate (MgTiO3) ceramics were synthesised using recycled magnesia-hercynite (MH) bricks as the raw materials to achieve solid waste reusing of cement kiln refractories. The recycled MH materials were mixed with anatase TiO2 to investigate the effect of addition of doped B2O3 during the synthesis of MgTiO3 ceramics at 1400 °C. Phase compositions and microstructural studies were performed using x-ray diffraction (XRD) and scanning electron microscope (SEM), respectively. In addition, energy-dispersive spectroscopy (EDS) was conducted and the dielectric properties of the samples were studied. Results show that the addition of B2O3 can promote sintering, improve shrinkage, promote densification, stabilise MgTiO3 lattice, and inhibit the formation of MgTiO3. In addition, the presence of appropriate amount of B2O3 can accelerate the material diffusion and result in grain growth through the formation of intercrystalline liquid phase. Results also suggest that an increase in dielectric constant results in a decrease in dielectric loss. It was concluded that 2 wt% was the optimum amount of B2O3 required to obtain the most favourable synthesis rate of MgTiO3 (98.2%). The samples exhibited a maximum density of 3.69 g·cm−3 and excellent microwave dielectric properties at ε r = 18.28 and tanδ = 0.086.

Application of Domain- and Genotype-Specific Models to Infer Post-Transcriptional Regulation of Segmentation Gene Expression in Drosophila

Unlike transcriptional regulation, the post-transcriptional mechanisms underlying zygotic segmentation gene expression in early Drosophila embryo have been insufficiently investigated. Condition-specific post-transcriptional regulation plays an important role in the development of many organisms. Our recent study revealed the domain- and genotype-specific differences between mRNA and the protein expression of Drosophila hb, gt, and eve genes in cleavage cycle 14A. Here, we use this dataset and the dynamic mathematical model to recapitulate protein expression from the corresponding mRNA patterns. The condition-specific nonuniformity in parameter values is further interpreted in terms of possible post-transcriptional modifications. For hb expression in wild-type embryos, our results predict the position-specific differences in protein production. The protein synthesis rate parameter is significantly higher in hb anterior domain compared to the posterior domain. The parameter sets describing Gt protein dynamics in wild-type embryos and Kr mutants are genotype-specific. The spatial discrepancy between gt mRNA and protein posterior expression in Kr mutants is well reproduced by the whole axis model, thus rejecting the involvement of post-transcriptional mechanisms. Our models fail to describe the full dynamics of eve expression, presumably due to its complex shape and the variable time delays between mRNA and protein patterns, which likely require a more complex model. Overall, our modeling approach enables the prediction of regulatory scenarios underlying the condition-specific differences between mRNA and protein expression in early embryo.