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Soyeong Jun, Hyeonseob Lim, Hoon Jang, Wookjae Lee, Jinwoo Ahn, Ji Hyun Lee, Duhee Bang
CRISPR/Cas9 for genome editing requires delivery of a guide RNA sequence and donor DNA for targeted homologous recombination. Typically, single-stranded oligodeoxynucleotide, serving as the donor template, and a plasmid encoding guide RNA are delivered as two separate components. However, in the multiplexed generation of single nucleotide variants, this two-component delivery system is limited by difficulty of delivering a matched pair of sgRNA and donor DNA to the target cell. Here, we describe a novel co-delivery system called "sgR-DNA" that uses a linearized double-stranded DNA consisting of donor DNA component and a component encoding sgRNA...
June 20, 2018: ACS Synthetic Biology
Antonin Desmecht, Timothy Steenhaut, Florence Pennetreau, Sophie Hermans, Olivier Riant
Polyamidoamine (PAMAM) dendrimers were covalently immobilized on multi-walled carbon nanotubes (MWNT) via two 'grafting to' strategies. We demonstrate the existence of non-covalent interactions between the two components but outline the superiority of our two grafting approaches, namely xanthate and click chemistry. MWNT surfaces were functionalized with activated ester and propargylic moieties prior to their reaction with PAMAM or azido-PAMAM dendrimers, respectively. The grafting of PAMAM generations 0 to 3 was evaluated with X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and transmission electron microscopy (TEM)...
June 20, 2018: Chemistry: a European Journal
Piia M Björn, Mikko Aro, Tuire Koponen, Lynn S Fuchs, Douglas Fuchs
Response to Intervention (RTI) was accepted in the early 2000s as a new framework for identifying learning difficulties (LD) in the U.S. In Finland, a similar multi-tiered framework has existed since 2010. In the present study, these frameworks are presented from the viewpoint of the role of assessment and instruction as expressed in documents that describe the frameworks, as it seems that these two components of RTI are the most disparate between the U.S. and Finland. We present a suggestion for the Finnish framework as an example of support in mathematics learning that incorporates principles of RTI (such as systematized assessment and instruction, cyclic support, and modifiable instruction)...
2018: Frontiers in Psychology
Peida Zhan, Manqian Liao, Yufang Bian
In joint models for item response times (RTs) and response accuracy (RA), local item dependence is composed of local RA dependence and local RT dependence. The two components are usually caused by the same common stimulus and emerge as pairs. Thus, the violation of local item independence in the joint models is called paired local item dependence. To address the issue of paired local item dependence while applying the joint cognitive diagnosis models (CDMs), this study proposed a joint testlet cognitive diagnosis modeling approach...
2018: Frontiers in Psychology
Anaïs Brosse, Maude Guillier
Small regulatory RNAs are now recognized as key regulators of gene expression in bacteria. They accumulate under specific conditions, most often because their synthesis is directly controlled by transcriptional regulators, including but not limited to alternative sigma factors and response regulators of two-component systems. In turn, small RNAs regulate, mostly at the posttranscriptional level, expression of multiple genes, among which are genes encoding transcriptional regulators. Small RNAs are thus embedded in mixed regulatory circuits combining transcriptional and posttranscriptional controls, and whose properties are discussed here...
May 2018: Microbiology Spectrum
Adriana Huerta-Viga, Linh-Lan Nguyen, Saeed Amirjalayer, Jamie H N Sim, Zhengyang Zhang, Howe-Siang Tan
Despite their extensive industrial usage, glass-forming liquids are not fully understood, and methods to investigate their dynamical heterogeneity are sought after. Here we show how the appearance of a second component in the visible absorption spectrum of a photosynthetic pigment upon cooling can be used to probe the glass transition of a dimethylsulfoxide-water mixture. The changes in the relative ratio of the two components with respect to temperature follow a sigmoid curve, and we show that the second component arises due to protonation of the pigment at low temperatures...
June 19, 2018: Physical Chemistry Chemical Physics: PCCP
Inês N Silva, Filipa D Pessoa, Marcelo J Ramires, Mário R Santos, Jörg D Becker, Vaughn S Cooper, Leonilde M Moreira
Bacteria from the Burkholderia cepacia complex grow in different natural and man-made environments and are feared opportunistic pathogens that cause chronic respiratory infections in cystic fibrosis patients. Previous studies showed that Burkholderia mucoid clinical isolates grown under stress conditions give rise to nonmucoid variants devoid of the exopolysaccharide cepacian. Here, we have determined that a major cause of the nonmucoid morphotype involves nonsynonymous mutations and small indels in the ompR gene encoding a response regulator of a two-component regulatory system...
June 18, 2018: Journal of Bacteriology
Toyotaka Sato, Tsukasa Shiraishi, Yoshiki Hiyama, Hiroyuki Honda, Masaaki Shinagawa, Masaru Usui, Koji Kuronuma, Naoya Masumori, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota
Colistin is a last-line drug for multidrug-resistant Gram-negative bacteria. We previously reported four plasmid-mediated colistin resistance ( mcr ) gene-negative colistin-resistant Escherichia coli clinical isolates, including the major pathogenic and fluoroquinolone-resistant strains O25b:H4-ST131- H 30Rx [isolates SRE34 and SRE44, minimum inhibitory concentration (MIC) for colistin = 16 mg/L] and non-x (SME296, MIC = 8 mg/L), and O18-ST416 (SME222, MIC = 4 mg/L). Herein, we investigated the colistin resistance mechanism, and identified novel amino acid substitutions or deletion in the PmrAB two-component system that activates eptA (encoding a phosphoethanolamine transferase) and arnT (encoding an undecaprenyl phosphate-alpha-4-amino-4-deoxy-l-arabinose arabinosyl transferase) in all colistin-resistant isolates...
June 18, 2018: Antimicrobial Agents and Chemotherapy
Yan Li, Ying Ru Loh, Alvin W Hung, CongBao Kang
Zika virus (ZIKV) protease is a two-component complex in which NS3 contains the catalytic triad and NS2B cofactor region is important for protease folding and activity. A protease construct-eZiPro lacking the transmembrane domains of NS2B was designed. Structural study on eZiPro reveals that the Thr-Gly-Lys-Arg (TGKR) sequence at the C-terminus of NS2B binds to the active site after cleavage. Another bZiPro construct only contains NS2B cofactor region and the N-terminus of NS3 without any artificial linker or protease cleavage site, giving rise to an empty pocket accessible to substrate and inhibitor binding...
June 13, 2018: Biochemical and Biophysical Research Communications
Bernie D Shizgal
This paper considers two nonequilibrium model systems described by linear Fokker-Planck equations for the time-dependent velocity distribution functions that yield steady state Kappa distributions for specific system parameters. The first system describes the time evolution of a charged test particle in a constant temperature heat bath of a second charged particle. The time dependence of the distribution function of the test particle is given by a Fokker-Planck equation with drift and diffusion coefficients for Coulomb collisions as well as a diffusion coefficient for wave-particle interactions...
May 2018: Physical Review. E
N A Olekhno, Y M Beltukov
Random impedance networks are widely used as a model to describe plasmon resonances in disordered metal-dielectric and other two-component nanocomposites. In the present work, the spectral properties of resonances in random networks are studied within the framework of the random matrix theory. We have shown that the appropriate ensemble of random matrices for the considered problem is the Jacobi ensemble (the MANOVA ensemble). The obtained analytical expressions for the density of states in such resonant networks show a good agreement with the results of numerical simulations in a wide range of metal filling fractions 0<p<1...
May 2018: Physical Review. E
Michelle Comas, Kristin Valentino, Anne F Johnson, Bradley S Gibson, Courtney Taylor
BACKGROUND AND OBJECTIVES: Overgeneral memory (OGM), difficulty in retrieving specific autobiographical memories, is a robust phenomenon related to the onset and course of depressive and posttraumatic stress disorders. Inhibitory mechanisms are theorized to underlie OGM; however, empirical support for this link is equivocal. The current study examines the differential roles of two aspects of inhibitory control in association with OGM: suppression of prepotent responses and resistance to proactive interference (PI)...
June 12, 2018: Journal of Behavior Therapy and Experimental Psychiatry
Ya-Sung Yang, Hsing-Yu Chen, Wei-Jane Hsu, Yu-Ching Chou, Cherng-Lih Perng, Hung-Sheng Shang, Yuan-Ting Hsiao, Jun-Ren Sun
OBJECTIVES: Tigecycline non-susceptible Acinetobacter nosocomialis (TNAN) have been discovered in clinical isolates. The resistance-nodulation-cell division (RND)-type efflux system plays a major role in tigecycline non-susceptible of Acinetobacter baumannii, but the mechanism in Acinetobacter nosocomialis remains unknown. Our aim was to analyze the contribution of efflux based tigecycline resistance in clinical A. nosocomialis isolates collected from multiple medical centers in Taiwan...
June 12, 2018: Clinical Microbiology and Infection
Aileen Y Chang, Edith C Tonui, Douglas Momanyi, Alex R Mills, Paul Wasike, Rakhi Karwa, Toby A Maurer, Sonak D Pastakia
INTRODUCTION: Compression therapy is well-established standard of care for chronic leg ulcers from venous disease and lymphedema. Chronic leg ulcers and lymphedema have a significant impact on quality of life, driven by pain, foul odor, and restricted mobility. Provision of layered compression therapy in resource-limited settings, as in Western Kenya and other regions of sub-Saharan Africa, is a major challenge due to several barriers: availability, affordability, and access to healthcare facilities...
June 15, 2018: Dermatology and Therapy
Megan A Catterton, Austin F Dunn, Rebecca R Pompano
Many in vivo tissue responses begin locally, yet most in vitro stimuli are delivered globally. Microfluidics has a unique ability to provide focal stimulation to tissue samples with precise control over fluid location, flow rate, and composition. However, previous devices utilizing fixed ports beneath the tissue required manual alignment of the tissue over the ports, increasing the risk of mechanical damage. Here we present a novel microfluidic device that allows the user to define the location of fluid delivery to a living tissue slice without manipulating the tissue itself...
June 15, 2018: Lab on a Chip
Mary Boyde, Emily Cooper, Hannah Putland, Rikki Stanton, Christie Harding, Ben Learmont, Clare Thomas, Jade Porter, Andrea Thompson, Louise Nicholls
BACKGROUND: Within nursing education, simulation has been recognised as an effective learning strategy. Embedding simulation within clinical units has the potential to enhance patient safety and improve clinical outcomes. However it is important to evaluate the effectiveness of this educational technique to support the actual value and effectiveness. OBJECTIVE: This study aimed to implement and evaluate an innovative simulation experience for registered nurses. METHODS: A high-fidelity simulation focusing on nursing assessment was conducted with 50 Registered Nurses in an Emergency Department (ED) at a large tertiary referral hospital...
June 5, 2018: Nurse Education Today
Xiaoliang Liu, Wei Zhou, Yudan Yang, Kang Cheng, Jincan Kang, Lei Zhang, Guoquan Zhang, Xiaojian Min, Qinghong Zhang, Ye Wang
The direct conversion of syngas into lower olefins is a highly attractive route for the synthesis of lower olefins. The selectivity of lower olefins via the conventional Fischer-Tropsch (FT) synthesis is restricted to ∼60% with high CH4 selectivity due to the limitation by the Anderson-Schulz-Flory (ASF) distribution. Here, we report the design of bifunctional catalysts for the direct conversion of syngas into lower olefins with selectivity significantly breaking the ASF distribution. The selectivity of C2 -C4 olefins reached 87% at a CO conversion of 10% and was sustained at 77% by increasing CO conversion to 29% over a bifunctional catalyst composed of Zn-doped ZrO2 nanoparticles and zeolite SSZ-13 nanocrystals...
May 28, 2018: Chemical Science
Alexander Crits-Christoph, Spencer Diamond, Cristina N Butterfield, Brian C Thomas, Jillian F Banfield
In soil ecosystems, microorganisms produce diverse secondary metabolites such as antibiotics, antifungals and siderophores that mediate communication, competition and interactions with other organisms and the environment1,2 . Most known antibiotics are derived from a few culturable microbial taxa 3 , and the biosynthetic potential of the vast majority of bacteria in soil has rarely been investigated 4 . Here we reconstruct hundreds of near-complete genomes from grassland soil metagenomes and identify microorganisms from previously understudied phyla that encode diverse polyketide and nonribosomal peptide biosynthetic gene clusters that are divergent from well-studied clusters...
June 13, 2018: Nature
Gina R Daniel, Caitlin E Pegg, Gregory A Smith
Herpesvirus particles have a complex architecture consisting of an icosahedral capsid that is surrounded by a lipid envelope. Connecting these two components is a layer of tegument that consists of varying amounts of twenty or more proteins. The arrangement of proteins within the tegument cannot easily be assessed and instead is inferred from tegument interactions identified in reductionist models. To better understand the tegument architecture, we have developed an approach to probe capsid-tegument interactions of extracellular viral particles by encoding tobacco etch virus (TEV) protease sites in viral structural proteins, along with distinct fluorescent tags in capsid and tegument components...
June 13, 2018: Journal of Virology
Erin Wall, Nadim Majdalani, Susan Gottesman
RcsB, a response regulator of the FixJ/NarL family, is at the center of a complex network of regulatory inputs and outputs. Cell surface stress is sensed by an outer membrane lipoprotein, RcsF, which regulates interactions of the inner membrane protein IgaA, lifting negative regulation of a phosphorelay. In vivo evidence supports a pathway in which histidine kinase RcsC transfers phosphate to phosphotransfer protein RcsD, resulting in phosphorylation of RcsB. RcsB acts either alone or in combination with RcsA to positively regulate capsule synthesis and synthesis of small RNA (sRNA) RprA as well as other genes, and to negatively regulate motility...
June 13, 2018: Annual Review of Microbiology
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