Applications of Catalytic Hairpin Assembly Reaction in Biosensing.

Nucleic acids are considered as perfect programmable materials for cascade signal amplification and not merely as genetic information carriers. Among them, catalytic hairpin assembly (CHA), an enzyme-free, high-efficiency, and isothermal amplification method, is a typical example. A typical CHA reaction is initiated by single-stranded analytes, and substrate hairpins are successively opened, resulting in thermodynamically stable duplexes. CHA circuits, which were first proposed in 2008, present dozens of systems today. Through in-depth research on mechanisms, the CHA circuits have been continuously enriched with diverse reaction systems and improved analytical performance. After a short time, the CHA reaction can realize exponential amplification under isothermal conditions. Under certain conditions, the CHA reaction can even achieve 600 000-fold signal amplification. Owing to its promising versatility, CHA is able to be applied for analysis of various markers in vitro and in living cells. Also, CHA is integrated with nanomaterials and other molecular biotechnologies to produce diverse readouts. Herein, the varied CHA mechanisms, hairpin designs, and reaction conditions are introduced in detail. Additionally, biosensors based on CHA are presented. Finally, challenges and the outlook of CHA development are considered

Methylation of CYP1A1 and VKORC1 promoter associated with stable dosage of warfarin in Chinese patients

Objective To investigate the association between DNA methylation and the stable warfarin dose through genome-wide DNA methylation analysis and pyrosequencing assay. Method This study included 161 patients and genome-wide DNA methylation analysis was used to screen potential warfarin dose-associated CpGs through Illumina Infinium HumanMethylation 450 K BeadChip; then, the pyrosequencing assay was used to further validate the association between the stable warfarin dose and alterations in the methylation of the screened CpGs. GenomeStudio Software and R were used to analyze the differentially methylated CpGs. Results The methylation levels of CpGs surrounding the xenobiotic response element (XRE) within the CYP1A1 promoter, differed significantly between the different dose groups (P  0, P < 0.05) with an increase in the stable dose of warfarin. At the VKORC1 promoter, two CpGs methylation levels were significantly different between the differential dose groups (P < 0.05), and one CpG (Chr16: 31106793) presented a significant negative correlation (r <  0, P <  0.05) among different dose (low, medium, and high) groups. Conclusion This is a novel report of the methylation levels of six CpGs surrounding the XRE within the CYP1A1 promoter and one differential CpG at the VKORC1 promoter associated with stable warfarin dosage; these methylation levels might be applied as molecular signatures for warfarin

Stochastic Stability of Discrete-Time Switched Systems with a Random Switching Signal

Necessary and sufficient condition for stochastic stability of discrete-time linear switched system with a random switching signal is considered in this paper, assuming that the switching signal allows fixed dwell time before a Markov switch occurs. It is shown that the stochastic stability of the system is equivalent to that of an auxiliary system with state transformations at switching time, whose switching signal is a Markov chain. The stochastic stability is studied using a stochastic Lyapunov approach. The effectiveness of the proposed approach is demonstrated by a numerical example

Solution-Processed Chitosan-Gated IZO-Based Transistors for Mimicking Synaptic Plasticity

Indium-zinc-oxide (IZO)-based electric double layer (EDL) transistors gated by solution-processed chitosan electrolyte films are fabricated on glass substrates and used for mimicking synaptic plasticity. The conductance of the self-assembled IZO channel tuned by the proton electrostatic modulation and electrochemical doping is regarded as the synaptic weight. Synaptic behaviors like paired-pulse facilitation and long-term potentiation are mimicked in the chitosan-gated IZO-based EDL transistor. Our results suggest that gate pulse amplitude and number have great influence on the synaptic plasticity transition

Solution scattering study of the <i>Bacillus subtilis</i> PgdS enzyme involved in poly-γ-glutamic acids degradation

<div><p>The PgdS enzyme is a poly-γ-glutamic (γ-PGA) hydrolase, which has potential application for a controllable degradation of γ-PGA by enzymatic depolymerization; however, the structure of PgdS is still unknown. Here, to study in detail the full-length PgdS structure, we analyze the low-resolution architecture of PgdS hydrolase from <i>Bacillus subtilis</i> in solution using small angle X-ray scattering (SAXS) method. Combining with other methods, like dynamic light scattering and mutagenesis analyses, a model for the full length structure and the possible substrate delivery route of PgdS are proposed. The results will provide useful hints for future investigations into the mechanisms of γ-PGA degradation by the PgdS hydrolase and may provide valuable practical information.</p></div

SAXS analyses of PgdS.

<p>SAXS scattering profiles and model reconstructions of PgdS at pH 6.0 (A), 5.0 (B) and 8.0 (C): black circle—experimental intensity; red line—smooth curve back transformed from the <i>p</i>(<i>r</i>) and extrapolated to zero scattering angle; green line—scattering pattern computed from the DAMMIF model; blue line—scattering pattern computed from the SASREF model; cyan line—scattering pattern computed from the CORAL model; magenta line—averaged scattering pattern calculated from the optimized models generated by EOM; lower left panel—distance distribution function <i>p(r)</i> for PgdS in solution. (D) normalized distance distribution functions for PgdS at pH 5.0 (black), pH 6.0 (green) and pH 8.0 (red).</p

Energy-Efficient Artificial Synapses Based on Flexible IGZO Electric-Double-Layer Transistors

Flexible low-voltage indium-gallium-zinc-oxide (IGZO) electric-double-layer transistors are fabricated on polyethylene terephthalate substrates at room temperature and proposed for energy-efficient artificial synapse application. The IGZO channel conductance and the gate voltage pulse are regarded as synaptic weight and synaptic spike, respectively. The energy consumption of our IGZO synaptic transistor is estimated to be as low as similar to 0.23 pJ/spike. Short-term synaptic plasticity and high-pass filtering behaviors are also mimicked in an individual IGZO synaptic transistor

Possible substrate delivery route.

<p>(A) Electrostatic potential properties of PgdS, which are contoured over the range ± 5 kT/e using DelPhi [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195355#pone.0195355.ref038" target="_blank">38</a>] within the PyMOL (<a href="http://www.pymol.sourceforge.net/" target="_blank">http://www.pymol.sourceforge.net/</a>) software (blue represents a positively charged surface region and red represents a negatively charged surface region). The green circles signify the interface between domain 2 and domain 3. (B) The mutation sites in the positively charged surface at the junction of domain 2 and domain 3. (C) Activity of PgdS wild type and mutants.</p

Multiple sequence alignment of three domains of PgdS and other NlpC/P60 domains.

<p>Three domains of PgdS, the NlpC/P60 catalytic domains of LytF, LytE and CwlS from <i>B</i>. <i>subtilis</i>, and putative lipoprotein Spr from <i>E</i>. <i>coli</i> (UniProt identifiers, <a href="http://www.uniprot.org/uniprot/P96740" target="_blank">P96740</a>, <a href="http://www.uniprot.org/uniprot/P54421" target="_blank">P54421</a>, <a href="http://www.uniprot.org/uniprot/O07532" target="_blank">O07532</a>, <a href="http://www.uniprot.org/uniprot/O31852" target="_blank">O31852</a> and P0AFV4) are aligned with MUSCLE [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195355#pone.0195355.ref027" target="_blank">27</a>] and edited by hand to match the structural similarity where appropriate by using ALINE [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0195355#pone.0195355.ref028" target="_blank">28</a>]. Identical and similar residues are highlighted in black and grey, respectivey. The secondary structure elements base on the domain 2 of PgdS, α-helices and β-strands are marked by red pillar and blue arrow, respectively. The strictly conserved cysteine/histidine/glutamine (asparagine or histidine) catalytic triad are marked with red triangles. Three conserved residues that contribute to the formation of catalytic core are also marked with red circles.</p