bluuebunny/crossref_metadata_2025 huggingface dataset:
Hit-and-run programming of therapeutic cytoreagents using mRNA nanocarriers
Authors: Moffett H. F. , Coon M. E. , Radtke S. , Stephan S. B. , McKnight L. , Lambert A. , Stoddard B. L. , Kiem H. P. , Stephan M. T.
Published: August 2017

Therapies based on immune cells have been applied for diseases ranging from cancer to diabetes. However, the viral and electroporation methods used to create cytoreagents are complex and expensive. Consequently, we develop targeted mRNA nanocarriers that are simply mixed with cells to reprogram them via transient expression. Here, we describe three examples to establish that the approach is simple and generalizable. First, we demonstrate that nanocarriers delivering mRNA encoding a genome-editing agent can efficiently knock-out selected genes in anti-cancer T-cells. Second, we imprint a long-lived phenotype exhibiting improved antitumor activities into T-cells by transfecting them with mRNAs that encode a key transcription factor of memory formation. Third, we show how mRNA nanocarriers can program hematopoietic stem cells with improved self-renewal properties. The simplicity of the approach contrasts with the complex protocols currently used to program therapeutic cells, so our methods will likely facilitate manufacturing of cytoreagents.
Variable repeats in the eukaryotic polyubiquitin gene ubi4 modulate proteostasis and stress survival
Authors: Gemayel Rita , Yang Yudi , Dzialo Maria C. , Kominek Jacek , Vowinckel Jakob , Saels Veerle , Van Huffel Leen , van der Zande Elisa , Ralser Markus , Steensels Jan , Voordeckers Karin , Verstrepen Kevin J.
Published: August 2017

Ubiquitin conjugation signals for selective protein degradation by the proteasome. In eukaryotes, ubiquitin is encoded both as a monomeric ubiquitin unit fused to a ribosomal gene and as multiple ubiquitin units in tandem. The polyubiquitin gene is a unique, highly conserved open reading frame composed solely of tandem repeats, yet it is still unclear why cells utilize this unusual gene structure. Using the Saccharomyces cerevisiae UBI4 gene, we show that this multi-unit structure allows cells to rapidly produce large amounts of ubiquitin needed to respond to sudden stress. The number of ubiquitin units encoded by UBI4 influences cellular survival and the rate of ubiquitin-proteasome system (UPS)-mediated proteolysis following heat stress. Interestingly, the optimal number of repeats varies under different types of stress indicating that natural variation in repeat numbers may optimize the chance for survival. Our results demonstrate how a variable polycistronic transcript provides an evolutionary alternative for gene copy number variation.
ATRX is a regulator of therapy induced senescence in human cells
Authors: Kovatcheva Marta , Liao Will , Klein Mary E. , Robine Nicolas , Geiger Heather , Crago Aimee M. , Dickson Mark A. , Tap William D. , Singer Samuel , Koff Andrew
Published: August 2017

Senescence is a state of stable cell cycle exit with important implications for development and disease. Here, we demonstrate that the chromatin remodeling enzyme ATRX is required for therapy-induced senescence. ATRX accumulates in nuclear foci and is required for therapy-induced senescence in multiple types of transformed cells exposed to either DNA damaging agents or CDK4 inhibitors. Mobilization into foci depends on the ability of ATRX to interact with H3K9me3 histone and HP1. Foci form soon after cells exit the cell cycle, before other hallmarks of senescence appear. Eliminating ATRX in senescent cells destabilizes the senescence-associated heterochromatic foci. Additionally, ATRX binds to and suppresses expression from the HRAS locus; repression of HRAS is sufficient to promote the transition of quiescent cells into senescence and preventing repression blocks progression into senescence. Thus ATRX is a critical regulator of therapy-induced senescence and acts in multiple ways to drive cells into this state.
Noninvasive Imaging of Ras Activity by Monomolecular Biosensor Based on Split-Luciferase Complementary Assay
Authors: Chen Liang , Leng Wei Bing , Li De Zhi , Xia Hong Wei , Ren Min , Tang Qiu Lin , Gong Qi Yong , Gao Fa Bao , Bi Feng
Published: August 2017

Deregulated activity of Ras GTPases has been observed in many types of human cancers, and contributes to the diverse aspects of carcinogenesis. Although the significance in tumorigenesis has been widely accepted and many therapeutic drugs are under development, little attention has been dedicated to the development of sensors for the Ras activity in vivo. Therefore, based on the split firefly luciferase complementation strategy, we developed a monomolecular bioluminescent biosensor to image endogenous Ras activity in living subject. In this biosensor, two inactive luciferase fragments are sandwiched by Raf-1, whose conformation changes upon GTP-Ras binding. Thus, the Ras activity can be surrogated by the intensity of the complementary luciferase. The bioluminescence analyses demonstrated that this novel biosensor behaved the robust and sensitive reporting efficiency in response to the dynamical changes of Ras activity, both in living colorectal cancer cells and in vivo. Compared to the traditional method, such as the pull-down assay, the bioluminescent sensor is simply, noninvasive, faster and more sensitive for the analysis of the endogenous Ras activity. This innovative work opens up the way for monitoring the preclinical curative effect and high-throughput screening of therapeutic drugs targeting Ras pathways.
Spatial effects in meta-foodwebs
Authors: Barter Edmund , Gross Thilo
Published: August 2017

In ecology it is widely recognised that many landscapes comprise a network of discrete patches of habitat. The species that inhabit the patches interact with each other through a foodweb, the network of feeding interactions. The meta-foodweb model proposed by Pillaiet al. combines the feeding relationships at each patch with the dispersal of species between patches, such that the whole system is represented by a network of networks. Previous work on meta-foodwebs has focussed on landscape networks that do not have an explicit spatial embedding, but in real landscapes the patches are usually distributed in space. Here we compare the dispersal of a meta-foodweb on Erdős-Rényi networks, that do not have a spatial embedding, and random geometric networks, that do have a spatial embedding. We found that local structure and large network distances in spatially embedded networks, lead to meso-scale patterns of patch occupation by both specialist and omnivorous species. In particular, we found that spatial separations make the coexistence of competing species more likely. Our results highlight the effects of spatial embeddings for meta-foodweb models, and the need for new analytical approaches to them.
The Diagnostic Value of Global Longitudinal Strain (GLS) on Myocardial Infarction Size by Echocardiography: A Systematic Review and Meta-analysis
Authors: Diao Kai-yue , Yang Zhi-gang , Ma Min , He Yong , Zhao Qin , Liu Xi , Gao Yue , Xie Lin-jun , Guo Ying-kun
Published: August 2017

A systematic review and meta-analysis of prospective randomized studies were performed to evaluate the diagnostic value of measuring global longitudinal strain (GLS) using speckle tracking echocardiography (STE) in determining myocardial infarction (MI) size, which is usually measured based on late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR). Eleven trials with a total of 765 patients were included. The pooled correlation was 0.70 (95% CI: 0.64, 0.74) between two-dimensional (2D) GLS and the LGE percentage, and it was 0.55 (95% CI: 0.19, 0.78) for three-dimensional (3D) GLS. Pooled diagnostic estimates for 2D GLS to differentiate an MI size >12% were as follows: sensitivity, 0.77 (95% CI: 0.61, 0.90); specificity, 0.86 (95% CI: 0.68, 0.96); positive likelihood ratio (PLR), 8.13 (95% CI: 1.90, 26.61); negative likelihood ratio (NLR), 0.28 (95% CI: 0.10, 0.54); and diagnostic odds ratio (DOR), 39.87 (95% CI: 4.12, 172.83). The estimated area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve was 0.702. The 2D STE results positively correlated with the infarction size quantified by CMR for patients who had experienced their first MI. This approach can serve as a good diagnostic index for assessing infarction area. However, more consolidated STE studies are still needed to determine the value of 3D STE.
Molecular determinants of proton selectivity and gating in the red-light activated channelrhodopsin Chrimson
Authors: Vierock Johannes , Grimm Christiane , Nitzan Noam , Hegemann Peter
Published: August 2017

Channelrhodopsins are light-gated ion channels of green algae used for the precise temporal and spatial control of transmembrane ion fluxes. The channelrhodopsin Chrimson from Chlamydomonas noctigama allows unprecedented deep tissue penetration due to peak absorption at 590 nm. We demonstrate by electrophysiological recordings and imaging techniques that Chrimson is highly proton selective causing intracellular acidification in HEK cells that is responsible for slow photocurrent decline during prolonged illumination. We localized molecular determinants of both high proton selectivity and red light activation to the extracellular pore. Whereas exchange of Glu143 only drops proton conductance and generates an operational Na-channel with 590 nm activation, exchange of Glu139 in addition increased the open state lifetime and shifted the absorption hypsochromic by 70 nm. In conjunction with Glu300 in the center and Glu124 and Glu125 at the intracellular end of the pore, Glu139 contributes to a delocalized activation gate and stabilizes by long-range interaction counterion configuration involving protonation of Glu165 that we identified as a key determinant of the large opsin shift in Chrimson.
Lipids, fatty acids and hydroxy-fatty acids of Euphausia pacifica
Authors: Yamada Hidetoshi , Yamazaki Yuya , Koike Seiji , Hakozaki Mayuka , Nagahora Nozomi , Yuki Sayaka , Yano Akira , Tsurumi Koichiro , Okumura Takuji
Published: August 2017

Euphausia pacifica is a good candidate for a resource of marine n-3 PUFA. However, few reports exist of the lipid and fatty acid composition of E. pacifica. To examine the potential of E. pacifica as a resource of marine n-3 PUFA, we analyzed E. pacifica oil. We extracted lipids from E. pacifica harvested from the Pacific Ocean near Sanriku, Japan. Lipid classes of E. pacifica oil were analyzed by TLC-FID and the fatty acid composition of the oil was analyzed by GC/MS. Free fatty acids and hydroxy-fatty acids were analyzed by LC/QTOFMS. The lipid content of E. pacifica ranged from 1.30% to 3.57%. The ratios of triacylglycerols, phosphatidylcholine, phosphatidylethanolamine and free fatty acids in E. pacifica lipids were 5.3–23.0%, 32.6–53.4%, 8.5–25.4% and 2.5–7.0%, respectively. The content of n-3 PUFA in E. pacifica lipids was 38.6–46.5%. We also showed that E. pacifica contains unusual fatty acids and derivatives: C16-PUFAs (9,12-hexadecadienoic acid, 6,9,12-hexadecatrienoic acid and 6,9,12,15-hexadecatetraenoic acid) and hydroxy-PUFAs (8-HETE and 10-HDoHE). E. pacifica is a good resource of marine n-3 PUFA. Moreover, E. pacifica can provide C16-PUFA and hydroxy-PUFAs.
Establishment of the most comprehensive ITS2 barcode database to date of the traditional medicinal plant Rhodiola (Crassulaceae)
Authors: Zhu Ruo-Wei , Li Yuan-Cong , Zhong Da-Lv , Zhang Jian-Qiang
Published: August 2017

The roots and rhizomes of Rhodiola crenulata and R. rosea have been used worldwide as adaptogens for hundreds of years. However, rapid growth in demand has resulted in merchants using other species of Rhodiola as adulterants. Here, we surveyed 518 individuals representing 47 of the 55 species in the genus, including 253 R. crenulata individuals from 16 populations and 98 R. rosea individuals from 11 populations, to evaluate the utility of the internal transcribed spacer 2 (ITS2) barcode for identification of Rhodiola species. We detected six haplotypes in R. crenulata and only one haplotype in R. rosea. An obvious overlap between intra- and inter-specific distance was detected, and the authentication efficacy of ITS2, which was assessed by BLAST1, a nearest distance method, and a tree test, was much lower than in other groups. However, R. crenulata and R. rosea could be exactly identified. Analysis showed that the secondary structure of ITS2 differs in R. crenulata and its closest relatives. Our results demonstrated that both a mini barcode from ITS2 and the structure of ITS2 are effective markers for the identification of R. crenulata and R. rosea. This study represents the most comprehensive database of ITS2 barcodes in Rhodiola to date and will be useful in Rhodiola species identification.
Characterizing particulate polycyclic aromatic hydrocarbon emissions from diesel vehicles using a portable emissions measurement system
Authors: Zheng Xuan , Wu Ye , Zhang Shaojun , Hu Jingnan , Zhang K. Max , Li Zhenhua , He Liqiang , Hao Jiming
Published: August 2017

Particulate polycyclic aromatic hydrocarbons (p-PAHs) emitted from diesel vehicles are of concern because of their significant health impacts. Laboratory tests, road tunnel and roadside experiments have been conducted to measure p-PAH emissions. While providing valuable information, these methods have limited capabilities of characterizing p-PAH emissions either from individual vehicles or under real-world conditions. We employed a portable emissions measurement (PEMS) to measure real-world emission factors of priority p-PAHs for diesel vehicles representative of an array of emission control technologies. The results indicated over 80% reduction in p-PAH emission factors comparing the China V and China II emission standard groups (113 μg kg−1 vs. 733 μg kg−1). The toxicity abatement in terms of Benzo[a]pyrene equivalent emissions was substantial because of the large reductions in highly toxic components. By assessing real traffic conditions, the p-PAH emission factors on freeways were lower than on local roads by 52% ± 24%. A significant correlation (R2~0.85) between the p-PAH and black carbon emissions was identified with a mass ratio of approximately 1/2000. A literature review indicated that diesel p-PAH emission factors varied widely by engine technology, measurement methods and conditions, and the molecular diagnostic ratio method for source apportionment should be used with great caution.
The effect of topical administration of cyclopentolate on ocular biometry: An analysis for mouse and human models
Authors: Huang Furong , Huang Shenghai , Xie Ruozhong , Yang Yanan , Yan Jiaofeng , Cao Xiaowen , Zhang Chunlan , Zhou Feng , Shen Meixiao , Qu Jia , Zhou Xiangtian
Published: August 2017

Mydriasis with muscarinic antagonists have been used routinely prior to retinal examination and sometimes prior to refractive measurements of the mouse eye. However, biometric changes during topical administration of muscarinic antagonists have not been fully investigated in mice and humans. We found that the mouse eyes treated with cyclopentolate developed a hyperopia with a reduction in both the vitreous chamber depth and axial length. In humans, prior to the cyclopentolate treatment, a 6D accommodative stimulus produced a myopic shift with a reduced anterior chamber depth, choroidal thickness and anterior lens radius of curvature and an increase in lens thickness. After the cyclopentolate treatment, human eyes developed a hyperopic shift with an increased anterior chamber depth and anterior lens radius of curvature and a reduced lens thickness. Therefore, the biometric changes associated with this hyperopic shift were mainly located in the posterior segment of the eye in mice. However, it is the anterior segment of the eye that plays a main role in the hyperopic shift in human subjects. These results further indicate that mouse eyes do not have accommodation which needs to be taken into account when they are used for the study of human refractive errors.
Targeted metabolome profiling by dual-probe microdialysis sampling and treatment using Gardenia jasminoides for rats with type 2 diabetes
Authors: Wang Lu , Pi Zifeng , Liu Shu , Liu Zhiqiang , Song Fengrui
Published: August 2017

Diabetes causes a variety of end-stage organ complications, including diabetic nephropathy. Metabolomics offers an approach for characterizing biofluid metabolic changes, but studies focusing on diabetic nephropathy are limited due to the loss of tissue-specific metabolic information. A microdialysis application for the sampling of intact endogenous metabolites has been developed, utilizing two probes simultaneously inserted into the kidney tissues and jugular vein of rats with type 2 diabetes. The comprehensive and quantitative analysis of 20 diagnostic biomarkers closely realated to type 2 diabetes and its complications were performed. Results indicated that amino acid and nucleotide levels were lower in diabetic rats, revealing that the metabolic pathways of amino acid, as well as purine and pyrimidine, were disturbed. Targeted metabolomics using mass spectrometry was performed to find potential therapeutic biomarkers and related metabolic pathways of Gardenia jasminoides (G. jasminoides) for treating diabetes. Results suggested that seven biomarkers in the kidney and five biomarkers in the blood were related to G. jasminoides. In addition, the marked perturbations of pathways were regulated after treatment with G. jasminoides, including amino acid metabolism and purine metabolism. These biomarkers and metabolic pathways provided new understanding for molecular mechanisms of G. jasminoides for treating diabetes and its complications.
A comprehensive analysis of the association of common variants of ABCG2 with gout
Authors: Yu Kuang-Hui , Chang Pi-Yueh , Chang Shih-Cheng , Wu-Chou Yah-Huei , Wu Li-An , Chen Ding-Pin , Lo Fu-Sung , Lu Jang-Jih
Published: August 2017

The objective of the present study was to determine whether there was an association between single nucleotide polymorphisms (SNPs) in ABCG2 and gout. We recruited 333 participants including 210 patients with gout and 123 controls and genotyped 45 SNPs in both cohorts. We found that 24 SNPs in ABCG2 are susceptibility loci associated with gout. Haplotype analysis revealed five blocks across the ABCG2 locus were associated with an increased risk of gout with odds ratios (ORs) from 2.59–3.17 (all P < 0.0001). A novel finding in the present study was the identification of rs3114018 in block 3 and its association with increased gout risk. We found that the rs2231142T allele in block 2 and the rs3114018C-rs3109823T (C-T) risk haplotype in block 3 conferred the greatest evidence of association to gout risk (P = 1.19 × 10−12 and P = 9.20 × 10−11, respectively). Our study provides an improved understanding of ABCG2 variations in patients with gout and, as shown by haplotype analysis, that ABCG2 may have a role in gout susceptibility.
Universal scaling of the self-field critical current in superconductors: from sub-nanometre to millimetre size
Authors: Talantsev E. F. , Crump W. P. , Tallon J. L.
Published: August 2017

Universal scaling behaviour in superconductors has significantly elucidated fluctuation and phase transition phenomena in these materials. However, universal behaviour for the most practical property, the critical current, was not contemplated because prevailing models invoke nucleation and migration of flux vortices. Such migration depends critically on pinning, and the detailed microstructure naturally differs from one material to another, even within a single material. Through microstructural engineering there have been ongoing improvements in the field-dependent critical current, thus illustrating its non-universal behaviour. But here we demonstrate the universal size scaling of the self-field critical current for any superconductor, of any symmetry, geometry or band multiplicity. Key to our analysis is the huge range of sample dimensions, from single-atomic-layer to mm-scale. These have widely variable microstructure with transition temperatures ranging from 1.2 K to the current record, 203 K. In all cases the critical current is governed by a fundamental surface current density limit given by the relevant critical field divided by the penetration depth.
Quantitative and organisational changes in mature extracellular matrix revealed through high-content imaging of total protein fluorescently stained in situ
Authors: Holdsworth Gill , Bon Hélène , Bergin Marianne , Qureshi Omar , Paveley Ross , Atkinson John , Huang Linghong , Tewari Roohi , Twomey Breda , Johnson Timothy
Published: August 2017

Fibrosis is a common driver of end-stage organ failure in most organs. It is characterised by excessive accumulation of extracellular matrix (ECM) proteins. Therapeutic options are limited and novel treatments are urgently required, however current cell-based high-throughput screening (HTS) models to identify molecules affecting ECM accumulation are limited in their relevance or throughput. We report a novel sensitive approach which combines in situ fluorescent staining of accumulated decellularised ECM proteins with automated high-content microscopy. Using this method to measure ECM accumulation in a kidney cell model, we demonstrated good agreement with established radiolabelled amino acid incorporation assays: TGFβ1 delivered a potent pro-fibrotic stimulus, which was reduced by TGFβ antibody or the anti-fibrotic nintedanib. Importantly, our method also provides information about matrix organisation: the extent of ECM accumulation was unaffected by the BMP antagonist Gremlin-1 but a pronounced effect on matrix fibrillar organisation was revealed. This rapid, straightforward endpoint provides quantitative data on ECM accumulation and offers a convenient cross-species readout that does not require antibodies. Our method facilitates discovery of novel pro- and anti-fibrotic agents in 384-well plate format and may be widely applied to in vitro cell-based models in which matrix protein deposition reflects the underlying biology or pathology.
Deciphering Clostridium metabolism and its responses to bioreactor mass transfer during syngas fermentation
Authors: Wan Ni , Sathish Ashik , You Le , Tang Yinjie J. , Wen Zhiyou
Published: August 2017

This study used 13C tracers and dynamic labeling to reveal metabolic features (nutrients requirements, pathway delineation and metabolite turnover rates) of Clostridium carboxidivorans P7, a model strain for industrial syngas fermentation, and its implication with bioreactor mass transfer. P7 shows poor activity for synthesizing amino acids (e.g., phenylalanine) and thus, needs rich medium for cell growth. The strain has multiple carbon fixation routes (Wood-Ljungdahl pathway, pyruvate:ferredoxin oxidoreductase reaction and anaplerotic pathways) and Re-citrate synthase (Ccar_06155) was a key enzyme in its tricarboxylic acid cycle (TCA) pathway. High fluxes were observed in P7’s Wood-Ljungdahl pathway, right branch of TCA cycle, pyruvate synthesis, and sugar phosphate pathways, but the cells anabolic pathways were strikingly slow. In bioreactor culture, when syngas flowrate increased from 1 to 10 mL/min, P7 strain produced same amount of total extracellular products (acids and alcohols) but high flowrate favored alcohol accumulation. This observation was due to the mass transfer limitation influencing energy metabolism (CO/H2 oxidation for cofactor generations) more prominently than carbon fixation. When syngas flowrate increased from 10 of 20 mL/min, the alcohol productivity was not improved and the labeling rate (~0.03 h−1) of key metabolite acetyl-CoA reached to P7 strain’s metabolism limitation regime.
Morphine activation of mu opioid receptors causes disinhibition of neurons in the ventral tegmental area mediated by β-arrestin2 and c-Src
Authors: Bull Fiona A. , Baptista-Hon Daniel T. , Lambert Jeremy J. , Walwyn Wendy , Hales Tim G.
Published: August 2017

The tyrosine kinase, c-Src, participates in mu opioid receptor (MOP) mediated inhibition in sensory neurons in which β-arrestin2 (β-arr2) is implicated in its recruitment. Mice lacking β-arr2 exhibit increased sensitivity to morphine reinforcement; however, whether β-arr2 and/or c-Src participate in the actions of opioids in neurons within the reward pathway is unknown. It is also unclear whether morphine acts exclusively through MOPs, or involves delta opioid receptors (DOPs). We examined the involvement of MOPs, DOPs, β-arr2 and c-Src in the inhibition by morphine of GABAergic inhibitory postsynaptic currents (IPSCs) recorded from neurons in the mouse ventral tegmental area. Morphine inhibited spontaneous IPSC frequency, mainly through MOPs, with only a negligible effect remaining in MOP−/− neurons. However, a reduction in the inhibition by morphine for DOP−/− c.f. WT neurons and a DPDPE-induced decrease of IPSC frequency revealed a role for DOPs. The application of the c-Src inhibitor, PP2, to WT neurons also reduced inhibition by morphine, while the inactive PP3, and the MEK inhibitor, SL327, had no effect. Inhibition of IPSC frequency by morphine was also reduced in β-arr2−/− neurons in which PP2 caused no further reduction. These data suggest that inhibition of IPSCs by morphine involves a β-arr2/c-Src mediated mechanism.
Multiple origins of endosymbionts in Chlorellaceae with no reductive effects on the plastid or mitochondrial genomes
Authors: Fan Weishu , Guo Wenhu , Van Etten James L. , Mower Jeffrey P.
Published: August 2017

Ancient endosymbiotic relationships have led to extreme genomic reduction in many bacterial and eukaryotic algal endosymbionts. Endosymbionts in more recent and/or facultative relationships can also experience genomic reduction to a lesser extent, but little is known about the effects of the endosymbiotic transition on the organellar genomes of eukaryotes. To understand how the endosymbiotic lifestyle has affected the organellar genomes of photosynthetic green algae, we generated the complete plastid genome (plastome) and mitochondrial genome (mitogenome) sequences from three green algal endosymbionts (Chlorella heliozoae, Chlorella variabilis and Micractinium conductrix). The mitogenomes and plastomes of the three newly sequenced endosymbionts have a standard set of genes compared with free-living trebouxiophytes, providing no evidence for functional genomic reduction. Instead, their organellar genomes are generally larger and more intron rich. Intron content is highly variable among the members of Chlorella, suggesting very high rates of gain and/or loss of introns during evolution. Phylogenetic analysis of plastid and mitochondrial genes demonstrated that the three endosymbionts do not form a monophyletic group, indicating that the endosymbiotic lifestyle has evolved multiple times in Chlorellaceae. In addition, M. conductrix is deeply nested within the Chlorella clade, suggesting that taxonomic revision is needed for one or both genera.
Flexible regulation of DNA displacement reaction through nucleic acid-recognition enzyme and its application in keypad lock system and biosensing
Authors: Li Chao , Shi Liu , Tao Yaqin , Mao Xiaoxia , Xiang Yang , Li Genxi
Published: August 2017

Toehold-mediated DNA strand displacement reaction (SDR) plays pivotal roles for the construction of diverse dynamic DNA nanodevices. To date, many elements have been introduced into SDR system to achieve controllable activation and fine regulation. However, as the most relevant stimuli for nucleic acid involved reaction, nucleic acid-recognizing enzymes (NAEs) have received nearly no attention so far despite SDR often takes place in NAEs-enriched environment (i.e., biological fluids). Herein, we report a set of NAEs-controlled SDR strategies, which take full advantage of NAEs’ properties. In this study, three different kinds of enzymes belonging to several classes (i.e., exonuclease, endonuclease and polymerase) have been used to activate or inhibit SDR, and more importantly, some mechanisms behind these strategies on how NAEs affect SDR have also been revealed. The exploration to use NAEs as possible cues to operate SDR will expand the available toolbox to build novel stimuli-fueled DNA nanodevices and could open the door to many applications including enzyme-triggered biocomputing and biosensing.
Effects of NRG1 Polymorphisms on Hirschsprung’s Disease Susceptibility: A Meta-analysis
Authors: Jiang Meng , Li Changli , Cao Guoqing , Yang Dehua , Zhang Xi , Yang Li , Li Shuai , Tang Shao-tao
Published: August 2017

Substantial resources have been devoted to evaluate the relationship between NRG1 variants rs7835688 and rs16879552 and Hirschsprung’s Disease (HSCR) but no consistency exists. This meta-analysis aimed to assess the association between the two SNPs and HSCR. PubMed, EMBASE, and Chinese Biological Medicine databases were searched for studies potentially eligible up to March, 2017. The summary odds ratios (ORs) with 95% CIs were calculated from different genetic models. Nine case-control studies (8 for both and 1 for rs16879552 only) involving 1984 HSCR patients and 4220 controls were identified. The combined results showed a significant association between HSCR risk and rs7835688 in all genetic models (per-allele model: OR = 1.66, 95% CI = 1.35–2.05; P = 1.940E-06). Rs16879552 was significantly associated with HSCR in per-allele (OR = 1.50, 95% CI = 1.27–1.76; P = 1.087E-06), additive and recessive model, except for dominant model. Stratified analysis by ethnicity showed that rs7835688 and rs16879552 were only causative for Asians, but not risk locus for Caucasians. Furthermore, pooled data based on segment length indicated that individuals with rs7835688 experienced a significantly higher risk for short-segment HSCR in all genotypes; but rs16879552 was only found to be associated with long-segment HSCR/ total colonic aganglionosis at the allele level.
Predicting synonymous codon usage and optimizing the heterologous gene for expression in E. coli
Authors: Tian Jian , Yan Yaru , Yue Qingxia , Liu Xiaoqing , Chu Xiaoyu , Wu Ningfeng , Fan Yunliu
Published: August 2017

Of the 20 common amino acids, 18 are encoded by multiple synonymous codons. These synonymous codons are not redundant; in fact, all of codons contribute substantially to protein expression, structure and function. In this study, the codon usage pattern of genes in the E. coli was learned from the sequenced genomes of E. coli. A machine learning based method, Presyncodon was proposed to predict synonymous codon selection in E. coli based on the learned codon usage patterns of the residue in the context of the specific fragment. The predicting results indicate that Presycoden could be used to predict synonymous codon selection of the gene in the E. coli with the high accuracy. Two reporter genes (egfp and mApple) were designed with a combination of low- and high-frequency-usage codons by the method. The fluorescence intensity of eGFP and mApple expressed by the (egfp and mApple) designed by this method was about 2.3- or 1.7- folds greater than that from the genes with only high-frequency-usage codons in E. coli. Therefore, both low- and high-frequency-usage codons make positive contributions to the functional expression of the heterologous proteins. This method could be used to design synthetic genes for heterologous gene expression in biotechnology.
Peripheral serotonin regulates postoperative intra-abdominal adhesion formation in mice
Authors: Bi Jianbin , Zhang Simin , Du Zhaoqing , Zhang Jia , Deng Yan , Liu Chang , Zhang Jingyao
Published: August 2017

The aim of the present study is to investigate the role and potential mechanisms of peripheral serotonin in postoperative intra-abdominal adhesion formation in mice. The caecum-rubbing operations were conducted for intra-abdominal adhesion formation modelling in wild-type and Tph1−/− mice. The deficiency of serotonin significantly decreased the adhesion scores, weight loss, and adhesion thickness as well as levels of collagen fibres and hydroxyproline in the adhesive tissues. The Tph1−/− mice exhibited a milder inflammatory response and oxidative stress in the adhesive tissues than did the wild-type mice. Moreover, the deficiency of serotonin reduced the levels of PAI-1 and fibrinogen, and raised the t-PA and t-PA/PAI levels in the peritoneal fluids. Moreover, the expressions of CD34, VEGF, TGF-β and 5-HT2B receptor in the adhesive tissues were significantly decreased in the Tph1−/− group mice. Furthermore, the Tph1−/− +5-HTP group showed more severe adhesions than did the Tph1−/− group mice, and the p-chlorophenylalanine (PCPA) could markedly alleviated the adhesion formation in the WT mice. In conclusion, the present study showed that peripheral serotonin regulated postoperative intra-abdominal adhesion formation by facilitating inflammation, oxidative stress, disorder of the fibrinolytic system, angiopoiesis and TGF-β1 expression via the 5-HT2B receptor in the adhesive tissues.
Nanocurcumin is superior to native curcumin in preventing degenerative changes in Experimental Cerebral Malaria
Authors: Dende Chaitanya , Meena Jairam , Nagarajan Perumal , Nagaraj Viswanathan Arun , Panda Amulya Kumar , Padmanaban Govindarajan
Published: August 2017

Curcumin has many pharmacological activities despite its poor bioavailability andin vivostability. Here, we show that a nanoformulated curcumin (PLGA-curcumin) has better therapeutic index than native curcumin in preventing the onset of neurological symptoms and delaying the death of mice in experimental cerebral malaria. Oral PLGA-curcumin was at least as effective as native curcumin at a 15-fold lower concentration in preventing the breakdown of blood-brain barrier and inhibition of brain mRNAs for inflammatory cytokines, chemokine receptor CXCR3 and its ligand CXCL10, with an increase in the anti-inflammatory cytokine IL-10. This was also reflected in serum cytokine and chemokine levels. At equivalent concentrations, a single oral dose of PLGA-curcumin was more effective in inhibiting serum IFNγ levels and enhancing IL-10 levels than native curcumin. Even at low concentrations, PLGA-curcumin was superior to native curcumin in inhibiting the sequestration of parasitized-RBCs and CD8+T cells in the brain. A single oral dose of 5 mg PLGA-curcumin containing 350 μg of curcumin resulted in 3–4 fold higher concentration and prolonged presence of curcumin in the brain than that obtained with 5 mg of native curcumin, indicating better bioavailability of PLGA-curcumin. PLGA-curcumin has potential as an adjunct drug to treat human cerebral malaria.
Association of leukocyte telomere length and the risk of age-related hearing impairment in Chinese Hans
Authors: Liu Han , Luo Huajie , Yang Tao , Wu Hao , Chen Dan
Published: August 2017

Age-related hearing loss (ARHI) is the most common sensory disorder in the elderly. Although telomere attrition has been shown as a determinant in the pathobiology of various age-related diseases, it remains unknown whether telomere length is associated with ARHI. We hypothesized that decreased leukocyte telomere length (LTL) increased the risk of ARHI. Thus, we measured LTL of 666 ARHI and 43 controls by an established quantitative PCR technique. Four audiogram shape subtypes of ARHI, including “flat shape (FL)”, “2–4 kHz abrupt loss (AL) shape”, “8 kHz dip (8D) shape” and “sloping shape (SL)” could be identified among the cases using K-means cluster analysis. Longer LTL was associated with the reduced incidence of ARHI (adjusted OR = 0.550, 95% CI: 0.420–0.721, P < 0.0001 for all the ARHI; 0.498, 0.318–0.780, P = 0.0023 for FL subgroup; 0.428, 0.292–0.628, P < 0.0001 for AL subgroup; 0.552, 0.399–0.764, P = 0.0003 for mSL subgroup). Subjects in the highest tertile of LTL were at less risk for ARHI than those in the lowest and middle tertiles (OR for ARHI: 0.327, 95% CI 0.170–0.629, P = 0.0008). There was a descending trend of LTL as the degree of pure tone threshold average (PTA) aggravated. These results suggest that telomere attrition may be involved in the progression of ARHI.
Asteroid surface impact sampling: dependence of the cavity morphology and collected mass on projectile shape
Authors: Cheng Bin , Yu Yang , Baoyin Hexi
Published: August 2017

In-situ exploration and remote thermal infrared observation revealed that a large fraction of Solar System small bodies should be covered with granular regolith. The complex and varied geology of the regolith layer may preserve the historical records of the surface modification and topographic evolution experienced by asteroids, especially cratering processes, in which the projectile shape plays a crucial role. Regarding the impact sampling scheme, the projectile-shape dependence of both the cavity morphology and the collected mass remains to be explored. This paper studies the process of the low-speed impact sampling on granular regolith using projectiles of different shapes. The results demonstrate that the projectile shape significantly influences the excavation stage, forming cavities with different morphologies, i.e., cone-shaped, bowl-shaped and U-shaped. We further indicate that the different velocity distributions of the ejecta curtains due to the various projectile shapes result in various amounts of collected mass in sampler canister, regarding which the 60° conical projectile exhibits preferable performance for impact sampling scheme. The results presented in this article are expected to reveal the dependence of the excavation process on projectile shape under micro gravity and provide further information on the optimal designs of impact sampling devices for future sample-return space missions.
CRISPR/Cas9-mediated mutagenesis of the dihydroflavonol-4-reductase-B (DFR-B) locus in the Japanese morning glory Ipomoea (Pharbitis) nil
Authors: Watanabe Kenta , Kobayashi Anna , Endo Masaki , Sage-Ono Kimiyo , Toki Seiichi , Ono Michiyuki
Published: August 2017

CRISPR/Cas9 technology is a versatile tool for targeted mutagenesis in many organisms, including plants. However, this technique has not been applied to the Japanese morning glory (Ipomoea [Pharbitis] nil), a traditional garden plant chosen for the National BioResource Project in Japan. We selected dihydroflavonol-4-reductase-B (DFR-B) of I. nil, encoding an anthocyanin biosynthesis enzyme, as the target gene, and changes in the stem colour were observed during the early stages of plant tissue culture by Rhizobium [Agrobacterium]-mediated transformation. Twenty-four of the 32 (75%) transgenic plants bore anthocyanin-less white flowers with bi-allelic mutations at the Cas9 cleavage site in DFR-B, exhibiting a single base insertion or deletions of more than two bases. Thus, these results demonstrate that CRISPR/Cas9 technology enables the exploration of gene functions in this model horticultural plant. To our knowledge, this report is the first concerning flower colour changes in higher plants using CRISPR/Cas9 technology.
A model to predict the incidence of allergic rhinitis based on meteorological factors
Authors: Ouyang Yuhui , Li Jin , Zhang Deshan , Fan Erzhong , Li Ying , Zhang Luo
Published: August 2017

Meteorological factors have been shown to affect the physiology, distribution, and amounts of inhaled allergens. The aim of this study was to develop a model to predict the trends for onset of allergic rhinitis (AR) patients. A total of 10,914 consecutive AR outpatients were assessed for the number of daily patient visits over a period of 4 years. Meteorological data were used to assess the relationship between meteorological factors and AR incidence by time-series data and regression analysis. Predictive models for incidence of AR were established in pollen-, dust mite- and mould-sensitive groups of patients, and the predictive performances of meteorological factors on the incidence of AR were estimated using root mean squared errors (RMSEs). The incidence of pollen-, dust mites- and mould-sensitive AR patients was significantly correlated with minimum temperature, vapour pressure, and sea-level pressure, respectively. The correlation between comprehensive meteorological parametric (CMP) and incidence of AR was higher than the correlation between the individual meteorological parameters and AR incidence. CMP had higher performance than individual meteorological parameters for predicting the incidence of AR patients. These findings suggest that the incidence of pollen-, dust mites- and mould-sensitive AR can be predicted employing models based on prevailing meteorological conditions.
Correction: Corrigendum: Phytosterol esters attenuate hepatic steatosis in rats with non-alcoholic fatty liver disease rats fed a high-fat diet
Authors: Song Lihua , Qu Dan , Zhang Qing , Jiang Jing , Zhou Haiyue , Jiang Rui , Li Yating , Zhang Yao , Yan Hongli
Published: August 2017

Scientific Reports 7: Article number: 41604; published online: 07 February 2017; updated: 24 August 2017. This Article contains an error in the order of the Figures. Figures 3, 4 and 6 were published as Figures 4, 6 and 3 respectively. The correct Figures 3, 4 and 6 appear below as Figures 1, 2 and 3 respectively.
Correction: Corrigendum: Demonstration of nanoimprinted hyperlens array for high-throughput sub-diffraction imaging
Authors: Byun Minseop , Lee Dasol , Kim Minkyung , Kim Yangdoo , Kim Kwan , Ok Jong G. , Rho Junsuk , Lee Heon
Published: August 2017

Scientific Reports 7: Article number: 46314; published online: 10 April 2017; updated: 24 August 2017. The original version of this Article contained an error in the spelling of the author Minseop Byun, which was incorrectly given as Minsueop Byun. This has now been corrected in the PDF and HTML versions of the Article.
Correction: Corrigendum: Pannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing
Authors: Chen Jin , Zhu Yan , Liang Chun , Chen Jing , Zhao Hong-Bo
Published: August 2017

Scientific Reports 5: Article number: 10762; published online: 02 June 2015; updated: 24 August 2017. This Article contains an error in Figure 1, where panel 1C was duplicated from Figure 1A in Reference 1. The correct Figure 1 appears below. All the other panels remain unchanged. The conclusions ofthe Article are unaffected by the correction of panel C.
Photoinduced reversible spin-state switching of an FeIII complex assisted by a halogen-bonded supramolecular network
Authors: Jeon Ie-Rang , Mathonière Corine , Clérac Rodolphe , Rouzières Mathieu , Jeannin Olivier , Trzop Elzbieta , Collet Eric , Fourmigué Marc
Published: August 2017

The organization of a molecular FeIII complex embedded in a halogen-bonded 2D network is chemically tuned to trigger temperature- and light-induced spin-state switching.
A naked-eye colorimetric sensor for Hg2+ monitoring with cascade signal amplification based on target-induced conjunction of split DNAzyme fragments
Authors: Chen Junhua , Pan Jiafeng , Chen Shu
Published: August 2017

We developed a naked-eye colorimetric sensor for Hg2+ monitoring with cascade signal amplification based on DNAzyme fragments and gold nanoparticles.
Synthesis of circular and triangular gold nanorings with tunable optical properties
Authors: Lin Xiaoying , Liu Yi , Lin Meihua , Zhang Qian , Nie Zhihong
Published: August 2017

This communication describes a robust wet-chemical synthetic strategy for the preparation of monodispersed circular and triangular gold nanorings.
Highlights from the 52nd EUCHEM conference on stereochemistry, Bürgenstock, Switzerland, May 2017
Authors: Montenegro Javier , Phipps Robert J.
Published: August 2017

The strong wind that was blowing in Brunnen on the 4th of May 2017 was prophetic of the storm of ideas and creativity that would later fall over the participants of the 52nd edition of the Bürgenstock conference.
pH-controlled crystal growth of copper/gemini surfactant complexes with bipyridine groups
Authors: Yao Junyao , Chen Qibin , Sheng Yujie , Kai Aiting , Liu Honglai
Published: August 2017

pH-controlled crystal growth of two copper complexes with different coordination modes is successfully manipulated by means of pH adjustment.
NMR spectroscopic studies of a TAT-derived model peptide in imidazolium-based ILs: influence on chemical shifts and the cis/trans equilibrium state
Authors: Wiedemann Christoph , Ohlenschläger Oliver , Mrestani-Klaus Carmen , Bordusa Frank
Published: August 2017

The impact of ionic liquids on the chemical shifts and the cis/trans equilibrium state of a model peptide was systematically investigated by NMR spectroscopy.
High temperature activation of hematite nanorods for sunlight driven water oxidation reaction
Authors: Ito Nathalie Minko , Carvalho Waldemir Moura , Muche Dereck Nills Ferreira , Castro Ricardo Hauch Ribeiro , Dalpian Gustavo Martini , Souza Flavio Leandro
Published: August 2017

An increase in processing temperatures gradually removes chlorine groups from the hematite re-activating its surface, which enhances the water oxidation efficiency.
Solvation of apolar compounds in protic ionic liquids: the non-synergistic effect of electrostatic interactions and hydrogen bonds
Authors: Sedov I. A. , Magsumov T. I. , Salikov T. M. , Solomonov B. N.
Published: August 2017

Protic ionic liquids can dissolve apolar compounds better than aprotic ionic liquids.
Non-fluorinated pre-irradiation-grafted (peroxidated) LDPE-based anion-exchange membranes with high performance and stability
Authors: Wang Lianqin , Brink Jethro J. , Liu Ye , Herring Andrew M. , Ponce-González Julia , Whelligan Daniel K. , Varcoe John R.
Published: August 2017

A radiation-grafted low density polyethylene-based anion-exchange membrane that is mechanically robust enough to routinely test in alkaline membrane fuel cells at 80 °C.
Immobilized bifunctional phosphonium salts as recyclable organocatalysts in the cycloaddition of CO2 and epoxides
Authors: Steinbauer J. , Longwitz L. , Frank M. , Epping J. , Kragl U. , Werner T.
Published: August 2017

An immobilized bifunctional phosphonium salt catalyst efficiently catalyzed the synthesis of cyclic carbonates under mild conditions, and was reused up to 15 times.
Adamantylated organosilatranes: design, synthesis, and potential appraisal in surface modification and anti-protozoal activity
Authors: Singh Gurjaspreet , Rani Sunita , Gawri Sanchita , Sinha Shweta , Sehgal Rakesh
Published: August 2017

A series of organosilatranes tethered with the privileged adamantane motif has been prepared and their pharmacokinetic profiles were scrutinized.
Scaling behavior of oxide-based electrothermal threshold switching devices
Authors: Li Dasheng , Goodwill Jonathan M. , Bain James A. , Skowronski Marek
Published: August 2017

Materials exhibiting insulator to metal transition (IMT) and transition metal oxides showing threshold switching behavior are considered as promising candidates for selector devices for crossbar non-volatile memory application.
Correction: Face and edge directed self-assembly of Pd12 tetrahedral nano-cages and their self-sorting
Authors: Howlader Prodip , Mukherjee Partha Sarathi
Published: August 2017

Correction for ‘Face and edge directed self-assembly of Pd12 tetrahedral nano-cages and their self-sorting’ by Prodip Howlader et al., Chem. Sci., 2016, 7, 5893–5899.
Additively manufactured artificial materials with metallic meta‐atoms
Authors: Zhang Shiyu , Whittow William , Vardaxoglou John (Yiannis) C.
Published: August 2017

This study presents the analysis and fabrication of artificial materials with metallic cuboid inclusions (termed here as meta‐atoms) in a dielectric host material. These synthetic materials or metamaterials have been additively manufactured with a fused deposition modelling three‐dimensional (3D) printer. The effective permittivity and permeability have been numerically analysed using the Maxwell–Garnett and Lewin's approximation. Simulations and measurements have shown good agreement with analytical calculations. The anisotropy of the heterogeneous mixture due to the orientation of the meta‐atoms has been demonstrated. The effective permittivity has been increased by the presence of the meta‐atoms, which has the potential of producing 3D‐printing metamaterials with tailored electromagnetic properties.