The bacterial antitoxin HipB establishes a ternary complex with operator DNA and phosphorylated toxin HipA to regulate bacterial persistence

Nearly all bacteria exhibit a type of phenotypic growth described as persistence that is thought to underlie antibiotic tolerance and recalcitrant chronic infections. The chromosomally encoded high-persistence (Hip) toxin-antitoxin proteins HipA(SO) and HipB(SO) from Shewanella oneidensis, a proteobacterium with unusual respiratory capacities, constitute a type II toxin-antitoxin protein module. Here we show that phosphorylated HipA(SO) can engage in an unexpected ternary complex with HipB(SO) and double-stranded operator DNA that is distinct from the prototypical counterpart complex from Escherichia coli. The structure of HipB(SO) in complex with operator DNA reveals a flexible C-terminus that is sequestered by HipA(SO) in the ternary complex, indicative of its role in binding HipA(SO) to abolish its function in persistence. The structure of HipA(SO) in complex with a non-hydrolyzable ATP analogue shows that HipA(SO) autophosphorylation is coupled to an unusual conformational change of its phosphorylation loop. However, HipA(SO) is unable to phosphorylate the translation factor Elongation factor Tu, contrary to previous reports, but in agreement with more recent findings. Our studies suggest that the phosphorylation state of HipA is an important factor in persistence and that the structural and mechanistic diversity of HipAB modules as regulatory factors in bacterial persistence is broader than previously thought

Experimental study on the response relationship between environmental DNA concentration and biomass of Schizothorax prenanti in still water

The superiority of the environmental DNA (eDNA) method for estimating the biomass of aquatic species has been demonstrated. However, the relationship between eDNA concentration and biomass is difficult to clarify under the influence of complex water flow and habitat conditions. It seriously restricts the popularization and application of the eDNA method in estimating aquatic biomass. In this paper, a typical fish species of rivers in southwest China, Schizothorax prenanti, was selected as the target species. Under standardized laboratory hydrostatic conditions, two environmental factors, water pH and water temperature were firstly determined through pre-experiments. Then we investigated the correlation between eDNA concentration and biomass under different body sizes and different body size compositions. The experimental results showed that water pH and the water temperature had a great influence on eDNA concentration. Therefore, the effects of these environmental factors need to be considered simultaneously when using eDNA concentration to estimate biomass. Under the premise of consistent environmental conditions, the biomass of Schizothorax prenanti was positively correlated with the eDNA concentration when the individual body size was the same. For each 1% increase in biomass of the fish, the eDNA concentration of adult (larger size) fish increased by 0.98%, while the eDNA concentration of juvenile (smaller size) fish increased by 1.38%. The smaller the size of individual fish, the greater the increase of eDNA concentration with biomass, and the increase of juvenile fish was about 1.4 times that the adult fish. When the biomass was the same but the body size composition was different, the higher the proportion of small body size individuals in the population, the higher the eDNA concentration. Special attention needs to be paid to the body size composition of the population to avoid the biomass estimation being lower than the actual value when the smaller size fish are dominant. The experimental results provide a strong basis for a more accurate estimation of aquatic biomass in reservoirs, lakes, and other still water areas by using the eDNA method

Structural basis of IL-23 antagonism by an Alphabody protein scaffold

Protein scaffolds can provide a promising alternative to antibodies for various biomedical and biotechnological applications, including therapeutics. Here we describe the design and development of the Alphabody, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold. We report affinity-matured Alphabodies with favourable physicochemical properties that can specifically neutralize human interleukin (IL)-23, a pivotal therapeutic target in autoimmune inflammatory diseases such as psoriasis and multiple sclerosis. The crystal structure of human IL-23 in complex with an affinity-matured Alphabody reveals how the variable interhelical groove of the scaffold uniquely targets a large epitope on the p19 subunit of IL-23 to harness fully the hydrophobic and hydrogen-bonding potential of tryptophan and tyrosine residues contributed by p19 and the Alphabody, respectively. Thus, Alphabodies are suitable for targeting protein-protein interfaces of therapeutic importance and can be tailored to interrogate desired design and binding-mode principles via efficient selection and affinity-maturation strategies

Mechanistic insight into how multidrug resistant Acinetobacter baumannii response regulator AdeR recognizes an intercistronic region

AdeR-AdeS is a two-component regulatory system, which controls expression of the adeABC efflux pump involved in Acinetobacter baumannii multidrug resistance. AdeR is a response regulator consisting of an N-terminal receiver domain and a C-terminal DNA-binding-domain. AdeR binds to a direct-repeat DNA in the intercistronic region between adeR and adeABC. We demonstrate a markedly high affinity binding between unphosphorylated AdeR and DNA with a dissociation constant of 20 nM. In addition, we provide a 2.75 angstrom crystal structure of AdeR DNA-binding-domain complexed with the intercistronic DNA. This structure shows that the alpha 3 and beta hairpin formed by beta 5-beta 6 interacts with the major and minor groove of the DNA, which in turn leads to the introduction of a bend. The AdeR receiver domain structure revealed a dimerization motif mediated by a gearwheel-like structure involving the D108F109-R122 motif through cation pi stack interaction. The structure of AdeR receiver domain bound with magnesium indicated a conserved Glu19Asp20-Asp63 magnesium-binding motif, and revealed that the potential phosphorylation site Asp63(OD1) forms a hydrogen bond with Lys112. We thus dissected the mechanism of how AdeR recognizes the intercistronic DNA, which leads to a diverse mode of response regulation. Unlocking the AdeRS mechanism provides ways to circumvent A. baumannii antibiotic resistance

Transmission ecosystems of Echinococcus multilocularis in China and Central Asia

From continental to regional scales, the zoonosis alveolar echinococcosis (AE) (caused by Echinococcus multilocularis) forms discrete patches of endemicity within which transmission hotspots of much larger prevalence may occur. Since the late 80s, a number of hotspots have been identified in continental Asia, mostly in China, wherein the ecology of intermediate host communities has been described. This is the case in south Gansu, at the eastern border of the Tibetan plateau, in south Ningxia, in the western Tian Shan of Xinjiang, and in the Alay valley of south Kyrgyzstan. Here we present a comparative natural history and characteristics of transmission ecosystems or ecoscapes. On this basis, regional types of transmission and their ecological characteristics have been proposed in a general framework. Combining climatic, land cover and intermediate host species distribution data, we identified and mapped 4 spatially distinct types of transmission ecosystems typified by the presence of one of the following small mammal ‘flagship' species: Ellobius tancrei, Ochotona curzoniae, Lasiopodomys brandtii or Eospalax fontanierii. Each transmission ecosystem had its own characteristics which can serve as a reference for further in-depth research in the transmission ecology of E. multilocularis. This approach may be used at fine spatial scales to characterize other poorly known transmission systems of the large Eurasian endemic zone, and help in consideration of surveillance systems and intervention

Emulsification properties of polysaccharides from Dioscorea opposita Thunb.

Peer reviewe

Chemical components and emulsification properties of mucilage from Dioscorea opposita Thunb

The properties of mucilage obtained from Dioscorea opposita, generated during industrial manufacturing were investigated in this study. Characteristics such as monosaccharide content, amino acid content, molecular weight, and structural features were measured, whereas morphology was observed using a scanning/transmission electron microscope. Additionally, emulsification properties at different concentrations (0.2%, 0.4%, 0.6%, 0.8%, and 1.0%) and under acidic and basic pH (5.0 and 9.0) conditions were studied. The results showed that emulsions prepared from mucilage and medium-chain triglycerides presented more effective emulsifying functions and higher stability, especially at low concentrations. Both, acidic and basic conditions improved the overall emulsification properties, which suggested that the isoelectric point of amino acids may be involved in the emulsification properties. The results of this study show that mucilage from Dioscorea opposita can be considered as a sustainable resource of a natural emulsifier obtained from industrial waste. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

CFD investigation of gas-solids flow in a new fluidized catalyst cooler

In our previous work, a new concept of annular catalyst cooler (ACC) was proposed and validated experimentally, which showed that an internal circulation of solids could be formed by using two gas distributors and both hydrodynamics and heat transfer could be largely improved. The current work simulated detailed hydrodynamics of gas-solids flow to advance our understanding of the ACC by using the two-fluid model. The influences of effective particle diameter dp⁎ and specularity coefficient φ were examined and compared with experimental data. Optimum values of dp⁎ = 170 μm and φ = 0.3 were determined and used in the simulations. Detailed hydrodynamics of gas-solids flow were then obtained, and the influential parameters were examined. The results showed that the proper selection of the ratio of gas velocities and the position of the heat transfer tube were needed to form a stable internal solids circulation in the ACC. The ACC had a combined hydrodynamic feature of up-flow and down-flow catalyst coolers with bigger solids volume fraction and smaller particle resident time, which are beneficial for improving the heat transfer between solids and wall

Strain-Controlled Spin Wave Excitation and Gilbert Damping in Flexible Co2FeSi Films Activated by Femtosecond Laser Pulse

The dynamic response of magnetic order to optical excitation at sub-picosecond scale has offered an intriguing alternative for magnetism manipulation. Such ultrafast optical manipulation of magnetism has become a fundamental challenging topic with high implications for future spintronics. Here, this study demonstrates such manipulation in Co2FeSi films grown on flexible polyimide substrate, and demonstrates how the magneto-optical interaction can be modified by using strain engineering which in turn triggers the excitation of both dipolar and exchange spin waves modes. Furthermore, Gilbert damping and spin-orbit coupling in Co2FeSi can both be tuned significantly by altering the magnitude and type of applied strain, suggesting an appealing way to manipulate spin wave propagation. These results develop the optical manipulation magnetism into the field of spin wave dynamics, and open a new direction in the application of spin orbitronics and magnonics devices using strain engineering