Revealing Key Interactions in a Metabolic Network: Model of Primary Phosphate Transport in Bacteria

One of the main problems of metabolic engineering is to determine the genetically controlled limiting links of a metabolic network. We have built a model of the primary transport of inorganic phosphates (P _i ), analyzed the P _i metabolic network in Gram-negative bacteria, and determined the factors controlling the phosphate exchange. The model explains why the P _i primary transport is not observed at the release stage. The nonlinearity of primary transport and the differences in its parameters in the membrane and within the cell give rise to transport asymmetry, i.e., the P _i release rate is low as compared with the uptake rate, and is small at the background of secondary transport. Discussed is a general scheme of coordination between primary and secondary transport, which are interconnected through the substrate–product relation.     

Anti‐inflammaging effects of human alpha‐1 antitrypsin

Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism underlying the anti‐aging effect of hAAT, we monitored the expression of aging‐associated genes and found that aging‐induced expressions of Relish (NF‐?B orthologue) and Diptericin were significantly lower in hAAT lines than in control lines. RNA‐seq analysis revealed that innate immunity genes regulated by NF‐kB were significantly and specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti‐inflammaging effect in human cells, we treated X‐ray‐induced senescence cells with hAAT and showed that hAAT treatment significantly decreased the expression and maturation of IL‐6 and IL‐8, two major factors of senescence‐associated secretory phenotype. Consistent with results from Drosophila,RNA‐seq analysis also showed that hAAT treatment significantly inhibited inflammation related genes and pathways. Together, our results demonstrated that hAAT significantly inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA‐approved drug with a confirmed safety profile, this novel therapeutic potential may make hAAT a promising candidate to combat aging and aging‐related diseases.     

Kinetics of rearrangement of solvation sheath of an excited molecule of the fluorescent probe 4"-dimethylaminochalcone

Processes accompanying the quenching of the fluorescent probe 4"-dimethylaminochalcone by hydroxyl groups of the proton-donor solvent 1-butanol have been studied. The kinetics of the deactivation of the excited state of 4"-dimethylaminochalcone has been monitored from the transition absorption spectra at a time resolution of 50 fs and fluorescence decay at a time resolution of 30 ps. The data obtained allow thinking that the next picture occurs in 1-butanol. At first stage, the 4"-dimethylaminochalcone molecule in its ground state forms a hydrogen bond with an alcohol molecule. At the second stage, the absorption of light quantum and corresponding rise of the dipole moment of 4"-dimethylaminochalcone take place, the initially existing hydrogen bond is retained. The third stage consists in the rearrangement of the 4"-dimethylaminochalcone solvation shell formed by alcohol dipole molecules due to an increase of the dipole of moment 4"-dimethylaminochalcone; this rearrangement takes an energy of about 24 kJ/mol, the arrangement time constant is close to 40 ps; the initial hydrogen bond is retained. The fourth stage involves processes that lead to fluorescence quenching; their time constant is about 200 ps. Taking into account that the quenching is a much slower process than the relaxation of the solvation shell, it was supposed that the quenching is not a direct consequence of the solvation shell relaxation or the existence of the hydrogen bond formed prior to excitation. Then the fluorescence quenching of 4"-dimethylaminochalcone can be accomplished through some other processes that are observed in other fluorescent molecules: (a) rearrangement of the initial hydrogen bond from a conformation that cannot quench the fluorescence of 4"-dimethylaminochalcone to a more "effective" conformation, (b) charge transfer between the excited of molecule 4"-dimethylaminochalcone and alcohol, or (c) solvent-induced twist of the 4"-dimethylaminochalcone amino group (its withdrawal from the molecule plane) by the action of the solvent.     

一些孟加拉当地产水果的抗氧化活性

研究了A. heterophyllus, A. squamosa, T. bellirica, S. samarangense, A. carambola and O. europa 水果的抗氧化活性。首先将这些成熟的水果切成小片,然后用日光晒干,最后用研磨器磨成粉末。这些水果粉末用99.99%的乙醇进行乙醇提取。这些提取物的活性通过其清除稳定的1, 1-diphenyl-2-picrylhydrazyl (DPPH)自由基的能力进行测定。实验结果表明,所有A. heterophyllus, A. squamosa, T. bellirica, S. samarangense, A. carambola and O. europa这些水果的乙醇提取物都具有抗氧化活性,这些水果的乙醇提取物的的IC₅₀值分别是410, 250, 34, 200, 30 和76μg/mL。其中A. carambola具有最高的抗氧化活性,其次是T. bellirica, O. europa, S. samarangense, A. squamosa 和 A. heterophyllus 。结果表明A. carambola, T. bellirica 和 O. europa对人体健康是非常有益的。     

An essential saccharide binding domain for the mAb 2C7 established for Neisseria gonorrhoeae LOS by ES-MS and MSn

A study of bacterial surface oligosaccharides were investigated among different strains of Neisseria gonorrhoeae to correlate structural features essential for binding to the MAb 2C7. This epitope is widely expressed and conserved in gonococcal isolates, characteristics essential to an effective candidate vaccine antigen. Sample lipooligosaccharides (LOS), was prepared by a modification of the hot phenol-water method from which de-O-acetylated LOS and oligosaccharide (OS) components were analyzed by ES-MS-CID-MS and ES-MSnin a triple quadrupole and an ion trap mass spectrometer, respectively. Previously documented natural heterogeneity was apparent from both LOS and OS preparations which was admixed with fragments induced by hydrazine and mild acid treatment. Natural heterogeneity was limited to phosphorylation and antenni extensions to the alpha-chain. Mild acid hydrolysis to release OS also hydrolyzed the beta(1-->6) glycosidic linkage of lipid A. OS structures were determined by collisional and resonance excitation combined with MS and multistep MSn which provided sequence information from both neutral loss, and nonreducing terminal fragments. A comparison of OS structures, with earlier knowledge of MAb binding, enzyme treatment, and partial acid hydrolysis indicates a generic overlapping domain for 2C7 binding. Reoccurring structural features include a Hepalpha(1-->3)Hepbeta(1-->5)KDO trisaccharide core branched on the nonreducing terminus (Hep-2) with an alpha(1-->2) linked GlcNAc (gamma-chain), and an alpha-linked lactose (beta-chain) residue. From the central heptose (Hep-1), a beta(1-->4) linked lactose (alpha-chain), moiety is required although extensions to this residue appear unnecessary.      

The Effects of Root Treatment with Various Stress Agents on Plant Cold- and Heat-Tolerance

The root systems of cucumber (Cucumis sativus L.), wheat (Triticum aestivum L.), and barley (Hordeum vulgare L.) plants were subjected to a short-term (6–7-h-long) treatment with low and high temperatures, sodium chloride, and lead nitrate, and the effect of these treatments on the changes in the cold- and heat-tolerance of leaf cells was determined. It was established that chilling of cucumber and wheat seedling roots at 10 and 2°C, respectively, or their heating at 38°C and 40°C, respectively, induced an increase in both cold- and heat-tolerance of leaf cells. An increase in the cold- and heat-tolerance was also observed in roots treated with sodium chloride at concentrations of 0.15 M (cucumber) and 0.2 M (wheat), as well as with lead nitrate at a concentration of 0.1 mM (barley, wheat). The tolerance increase induced by these stress agents was accompanied by a considerable increase in the ABA concentration in leaves. The effect of physical and chemical stress agents is suggested to induce the same nonspecific changes in the aboveground organs. These changes bring about, directly or indirectly, an increase in the cold- and heat-tolerance and are related to an increase in the ABA content.     

<Emphasis Type="Italic">Setaria Viridis</Emphasis> tolerance of high zinc concentrations

The effect of high zinc concentrations on the growth and photosynthetic apparatus of Setaria viridis (L.) Beauv. was investigated under laboratory conditions and a vegetation experiment. The experiments showed that zinc concentrations of 10⁻⁶ to 10⁻³ M did not influence seed germination. Moreover, zinc in concentrations of 40 and 80 mg kg substrate had no significant effect on most of the plant growth parameters. However, higher metal concentrations (160 and 320 mg kg substrate) inhibited shoot biomass, leaf area, inflorescence length, and biomass. At the same time, parameters such as the content of chlorophyll (a + b), F ₀, F_v, and the F_v/F_m rate were not reduced even in the presence of zinc in the highest concentrations (320 mg kg substrate). S. viridis tolerance of high zinc concentrations, as well as its capacity to accumulate zinc in roots and shoots, suggests the plant can be used for phytoremediation of zinc polluted soils.     

Effect of a DC external electric field on the properties of a nonuniform microwave discharge in hydrogen at reduced pressures

The effect of a dc external electrical field on the properties of a highly nonuniform electrode microwave discharge in hydrogen at a pressure of 1 Torr was studied using optical emission spectroscopy and selfconsistent two-dimensional simulations. It is shown that the negative voltage applied to the antenna electrode with respect to the grounded chamber increases the discharge radiation intensity, while the positive voltage does not affect the discharge properties. The simulation results agree well with the experimental data.