132 research outputs found

    Computational identification of rare codons of Escherichia coli based on codon pairs preference

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    <p>Abstract</p> <p>Background</p> <p>Codon bias is believed to play an important role in the control of gene expression. In <it>Escherichia coli</it>, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not been well established. Here we focus on the patterns of rarely-used synonymous codons. A novel method was introduced to identify the rare codons merely by codon pair bias in <it>Escherichia coli</it>.</p> <p>Results</p> <p>In <it>Escherichia coli</it>, we defined the "rare codon pairs" by calculating the frequency of occurrence of all codon pairs in coding sequences. Rare codons which are disliked in genes could make great contributions to forming rare codon pairs. Meanwhile our investigation showed that many of these rare codon pairs contain termination codons and the recognized sites of restriction enzymes. Furthermore, a new index (F<sub>rare</sub>) was developed. Through comparison with the classical indices we found a significant negative correlation between F<sub>rare </sub>and the indices which depend on reference datasets.</p> <p>Conclusions</p> <p>Our approach suggests that we can identify rare codons by studying the context in which a codon lies. Also, the frequency of rare codons (F<sub>rare</sub>) could be a useful index of codon bias regardless of the lack of expression abundance information.</p

    Promoting Cardiac Repair through Simple Engineering of Nanoparticles with Exclusive Targeting Capability toward Myocardial Reperfusion Injury by Thermal Resistant Microfluidic Platform

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    Nanoparticle (NP)-based intravenous administration represents the most convenient cardiac targeting delivery routine, yet, there are still therapeutic issues due to the lack of targeting efficiency and specificity. Active targeting methods using functionalization of ligands onto the NPs' surface may be limited by trivial modification procedures and reduced targeting yield in vivo. Here, a microfluidics assisted single step, green synthesis method is introduced for producing targeting ligands free heart homing NPs in a tailored manner. The generated beta-glucan-based NPs exhibit precise and efficient targeting capability toward Dectin-1(+) monocytes/macrophages, which are confirmed as main pathogenesis mediators for cardiac ischemic/reperfusion (I/R) injury, with a sequentially enhanced cardiac NP accumulation, and this targeting strategy is exclusively suitable for cardiac I/R but not for other cardiovascular diseases, as confirmed both in murine and human model. Comparing to FDA-approved nano-micelles formulation, beta-glucan NPs loaded with NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome inhibitor (CY-09) exhibit better efficiency in ameliorating myocardial injury and heart failure induced by surgically induced I/R. These findings indicate a simple production of targeting-ligand free NPs, and demonstrate their potential therapeutic applications for preclinical I/R-induced cardiac injury amelioration.Peer reviewe

    Tandem-Mass-Tag based proteomic analysis facilitates analyzing critical factors of porous silicon nanoparticles in determining their biological responses under diseased condition

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    The analysis of nanoparticles' biocompatibility and immunogenicity is mostly performed under a healthy condition. However, more clinically relevant evaluation conducted under pathological condition is less known. Here, the immunogenicity and bio-nano interactions of porous silicon nanoparticles (PSi NPs) are evaluated in an acute liver inflammation mice model. Interestingly, a new mechanism in which PSi NPs can remit the hepatocellular damage and inflammation activation in a surface dependent manner through protein corona formation, which perturbs the inflammation by capturing the pro-inflammatory signaling proteins that are inordinately excreted or exposed under pathological condition, is found. This signal sequestration further attenuates the nuclear factor kappa B pathway activation and cytokines production from macrophages. Hence, the study proposes a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological conditions, which might further offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease-specific or personalized manner.Peer reviewe

    Anomalous stopping of laser-accelerated intense proton beam in dense ionized matter

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    Ultrahigh-intensity lasers (1018^{18}-1022^{22}W/cm2^{2}) have opened up new perspectives in many fields of research and application [1-5]. By irradiating a thin foil, an ultrahigh accelerating field (1012^{12} V/m) can be formed and multi-MeV ions with unprecedentedly high intensity (1010^{10}A/cm2^2) in short time scale (∼\simps) are produced [6-14]. Such beams provide new options in radiography [15], high-yield neutron sources [16], high-energy-density-matter generation [17], and ion fast ignition [18,19]. An accurate understanding of the nonlinear behavior of beam transport in matter is crucial for all these applications. We report here the first experimental evidence of anomalous stopping of a laser-generated high-current proton beam in well-characterized dense ionized matter. The observed stopping power is one order of magnitude higher than single-particle slowing-down theory predictions. We attribute this phenomenon to collective effects where the intense beam drives an decelerating electric field approaching 1GV/m in the dense ionized matter. This finding will have considerable impact on the future path to inertial fusion energy.Comment: 8 pages, 4 figure
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