bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming mcr-1 mediated colistin resistance with colistin in combination with other antibiotics
Authors: MacNair Craig R. , Stokes Jonathan M. , Carfrae Lindsey A. , Fiebig-Comyn Aline A. , Coombes Brian K. , Mulvey Michael R. , Brown Eric D. 
Published: January 2018

AbstractPlasmid-borne colistin resistance mediated by mcr-1 may contribute to the dissemination of pan-resistant Gram-negative bacteria. Here, we show that mcr-1 confers resistance to colistin-induced lysis and bacterial cell death, but provides minimal protection from the ability of colistin to disrupt the Gram-negative outer membrane. Indeed, for colistin-resistant strains of Enterobacteriaceae expressing plasmid-borne mcr-1, clinically relevant concentrations of colistin potentiate the action of antibiotics that, by themselves, are not active against Gram-negative bacteria. The result is that several antibiotics, in combination with colistin, display growth-inhibition at levels below their corresponding clinical breakpoints. Furthermore, colistin and clarithromycin combination therapy displays efficacy against mcr-1-positive Klebsiella pneumoniae in murine thigh and bacteremia infection models at clinically relevant doses. Altogether, these data suggest that the use of colistin in combination with antibiotics that are typically active against Gram-positive bacteria poses a viable therapeutic alternative for highly drug-resistant Gram-negative pathogens expressing mcr-1.
Engineering yeast for the production of breviscapine by genomic analysis and synthetic biology approaches
Authors: Liu Xiaonan , Cheng Jian , Zhang Guanghui , Ding Wentao , Duan Lijin , Yang Jing , Kui Ling , Cheng Xiaozhi , Ruan Jiangxing , Fan Wei , Chen Junwen , Long Guangqiang , Zhao Yan , Cai Jing , Wang Wen , Ma Yanhe , Dong Yang , Yang Shengchao , Jiang Huifeng 
Published: January 2018

AbstractThe flavonoid extract from Erigeron breviscapus, breviscapine, has increasingly been used to treat cardio- and cerebrovascular diseases in China for more than 30 years, and plant supply of E. breviscapus is becoming insufficient to satisfy the growing market demand. Here we report an alternative strategy for the supply of breviscapine by building a yeast cell factory using synthetic biology. We identify two key enzymes in the biosynthetic pathway (flavonoid-7-O-glucuronosyltransferase and flavone-6-hydroxylase) from E. breviscapus genome and engineer yeast to produce breviscapine from glucose. After metabolic engineering and optimization of fed-batch fermentation, scutellarin and apigenin-7-O-glucuronide, two major active ingredients of breviscapine, reach to 108 and 185 mg l–1, respectively. Our study not only introduces an alternative source of these valuable compounds, but also provides an example of integrating genomics and synthetic biology knowledge for metabolic engineering of natural compounds.
Control of cell morphology and differentiation by substrates with independently tunable elasticity and viscous dissipation
Authors: Charrier Elisabeth E. , Pogoda Katarzyna , Wells Rebecca G. , Janmey Paul A. 
Published: January 2018

AbstractThe mechanical properties of extracellular matrices can control the function of cells. Studies of cellular responses to biomimetic soft materials have been largely restricted to hydrogels and elastomers that have stiffness values independent of time and extent of deformation, so the substrate stiffness can be unambiguously related to its effect on cells. Real tissues, however, often have loss moduli that are 10 to 20% of their elastic moduli and behave as viscoelastic solids. The response of cells to a time-dependent viscous loss is largely uncharacterized because appropriate viscoelastic materials are lacking for quantitative studies. Here we report the synthesis of soft viscoelastic solids in which the elastic and viscous moduli can be independently tuned to produce gels with viscoelastic properties that closely resemble those of soft tissues. Systematic alteration of the hydrogel viscosity demonstrates the time dependence of cellular mechanosensing and the influence of viscous dissipation on cell phenotype.
A phenotype centric benchmark of variant prioritisation tools
Authors: Anderson Denise , Lassmann Timo 
Published: January 2018

AbstractNext generation sequencing is a standard tool used in clinical diagnostics. In Mendelian diseases the challenge is to discover the single etiological variant among thousands of benign or functionally unrelated variants. After calling variants from aligned sequencing reads, variant prioritisation tools are used to examine the conservation or potential functional consequences of variants. We hypothesised that the performance of variant prioritisation tools may vary by disease phenotype. To test this we created benchmark data sets for variants associated with different disease phenotypes. We found that performance of 24 tested tools is highly variable and differs by disease phenotype. The task of identifying a causative variant amongst a large number of benign variants is challenging for all tools, highlighting the need for further development in the field. Based on our observations, we recommend use of five top performers found in this study (FATHMM, M-CAP, MetaLR, MetaSVM and VEST3). In addition we provide tables indicating which analytical approach works best in which disease context. Variant prioritisation tools are best suited to investigate variants associated with well-studied genetic diseases, as these variants are more readily available during algorithm development than variants associated with rare diseases. We anticipate that further development into disease focussed tools will lead to significant improvements.
Transcriptomic responses to biotic stresses in Malus x domestica: a meta-analysis study
Authors: Balan Bipin , Marra Francesco Paolo , Caruso Tiziano , Martinelli Federico 
Published: January 2018

AbstractRNA-Seq analysis is a strong tool to gain insight into the molecular responses to biotic stresses in plants. The objective of this work is to identify specific and common molecular responses between different transcriptomic data related to fungi, virus and bacteria attacks in Malus x domestica. We analyzed seven transcriptomic datasets in Malus x domestica divided in responses to fungal pathogens, virus (Apple Stem Grooving Virus) and bacteria (Erwinia amylovora). Data were dissected using an integrated approach of pathway- and gene- set enrichment analysis, Mapman visualization tool, gene ontology analysis and inferred protein-protein interaction network. Our meta-analysis revealed that the bacterial infection enhanced specifically genes involved in sugar alcohol metabolism. Brassinosteroids were upregulated by fungal pathogens while ethylene was highly affected by Erwinia amylovora. Gibberellins and jasmonates were strongly repressed by fungal and viral infections. The protein-protein interaction network highlighted the role of WRKYs in responses to the studied pathogens. In summary, our meta-analysis provides a better understanding of the Malus X domestica transcriptome responses to different biotic stress conditions; we anticipate that these insights will assist in the development of genetic resistance and acute therapeutic strategies. This work would be an example for next meta-analysis works aiming at identifying specific common molecular features linked with biotic stress responses in other specialty crops.
Identification of valid reference genes for mRNA and microRNA normalisation in prostate cancer cell lines
Authors: Zhao Hui , Ma Teng-Fei , Lin Jie , Liu Lin-Lin , Sun Wei-Jie , Guo Li-Xia , Wang Si-Qi , Otecko Newton O. , Zhang Ya-Ping 
Published: January 2018

AbstractRT-qPCR offers high sensitivity, for accurate interpretations of qPCR results however, normalisation using suitable reference genes is fundamental. Androgens can regulate transcriptional expression including reference gene expression in prostate cancer. In this study, we evaluated ten mRNA and six non-protein coding RNA reference genes in five prostate cell lines under varied dihydrotestosterone (DHT) treatments. We validated the effects of DHT-treatments using media containing charcoal-stripped serum prior to DHT stimulation on the test samples by Western blot experiments. Reference gene expression stability was analysed using three programs (geNorm, NormFinder and BestKeeper), and the recommended comprehensive ranking is provided. Our results reveal thatACTBandGAPDH, andmiR-16andmiR-1228-3pare the most suitable mRNA and miRNA reference genes across all cell lines, respectively. Considering prostate cancer cell types,ACTB/GAPDHandACTB/HPRT1are the most suitable reference gene combinations for mRNA analysis, andmiR-16/miR-1228-3pandRNU6-2/RNU43for miRNA analysis in AR+, and AR− and normal cell lines, respectively. Comparison of relative target gene (PCA3andmiR-141) expression reveals different patterns depending on reference genes used for normalisation. To our knowledge, this is the first report on validation of reference genes under different DHT treatments in prostate cancer cells. This study provides insights for discovery of reliable DHT-regulated genes in prostate cells.
A comparative Study of Aptasensor Vs Immunosensor for Label-Free PSA Cancer Detection on GQDs-AuNRs Modified Screen-Printed Electrodes
Authors: Srivastava Monika , Nirala Narsingh R. , Srivastava S. K. , Prakash Rajiv 
Published: January 2018

AbstractLabel-free and sensitive detection of PSA (Prostate Specific Antigen) is still a big challenge in the arena of prostate cancer diagnosis in males. We present a comparative study for label-free PSA aptasensor and PSA immunosensor for the PSA-specific monoclonal antibody, based on graphene quantum dots-gold nanorods (GQDs-AuNRs) modified screen-printed electrodes. GQDs-AuNRs composite has been synthesized and used as an electro-active material, which shows fast electron transfer and catalytic property. Aptamer or anti-PSA has immobilized onto the surface of modified screen printed electrodes. Three techniques are used simultaneously, viz. cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedence spectroscopy (EIS) to investigate the analytical performance of both PSA aptasensor and PSA immunosensor with its corresponding PSA antigen. Under optimum conditions, both sensors show comparable results with an almost same limit of detection (LOD) of 0.14 ng mL−1. The results developed with aptasensor and anti-PSA is also checked through the detection of PSA in real samples with acceptable results. Our study suggests some advantages of aptasensor in terms of better stability, simplicity and cost effectiveness. Further our present work shows enormous potential of our developed sensors for real application using voltammetric and EIS techniques simultaneous to get reliable detection of the disease.
Locating Order-Disorder Phase Transition in a Cardiac System
Authors: Ashikaga Hiroshi , Asgari-Targhi Ameneh 
Published: January 2018

AbstractTo prevent sudden cardiac death, predicting where in the cardiac system an order-disorder phase transition into ventricular fibrillation begins is as important as when it begins. We present a computationally efficient, information-theoretic approach to predicting the locations of the wavebreaks. Such wavebreaks initiate fibrillation in a cardiac system where the order-disorder behavior is controlled by a single driving component, mimicking electrical misfiring from the pulmonary veins or from the Purkinje fibers. Communication analysis between the driving component and each component of the system reveals that channel capacity, mutual information and transfer entropy can locate the wavebreaks. This approach is applicable to interventional therapies to prevent sudden death, and to a wide range of systems to mitigate or prevent imminent phase transitions.
TT(N)mGCCTC inhibits archaeal family B DNA polymerases
Authors: Sun Shuhui , Guo Wei , Yang Jin-Shu , Qiu Mengsheng , Zhu Xiao-Jing , Dai Zhong-Min 
Published: January 2018

AbstractThe proofreading activity of the archaeal family B DNA polymerases enables PCR with high fidelity. However, thermostable proofreading DNA polymerases occasionally failed to amplify target fragment that could be amplified by Taq DNA polymerase. We have previously showed that G-rich sequences, which form G-quadruplex, can bind to and inhibit proofreading DNA polymerases. Here we showed that single-stranded oligonucleotides containing sequences of TT(N)mGCCTC can bind and inhibit archaeal family B DNA polymerases but not Taq DNA polymerase. It is very likely that TT(N)mGCCTC inhibits thermostable DNA polymerases during PCR in a single-stranded form. To the best of our knowledge, this is the first example of DNA sequence that could inhibit DNA polymerase in its single-stranded form.
Development and validation of risk prediction models for cardiovascular mortality in Chinese people initialising peritoneal dialysis: a cohort study
Authors: Yu Dahai , Cai Yamei , Chen Ying , Chen Tao , Qin Rui , Zhao Zhanzheng , Simmons David 
Published: January 2018

AbstractCardiovascular disease is the leading cause of death among patients receiving peritoneal dialysis. We aimed to develop and validate a risk prediction model for cardiovascular death within 2 years after the initiation of peritoneal dialysis (PD). A cohort including all patients registered with the Henan Peritoneal Dialysis Registry (HPDR) between 2007 and 2014. Multivariate logistic regression analysis was used to develop the risk prediction model. The HPDR data was randomly divided into two cohorts with 60% (1,835 patients) for model derivation, and 40% (1,219 patients) for model validation. The absolute rate of cardiovascular mortality was 14.2% and 14.4 in the derivation and validation cohort, respectively. Age, body mass index, blood pressure, serum lipids, fasting glucose, sodium, albumin, total protein, and phosphorus were the strongest predictors of cardiovascular mortality in the final model. Discrimination of the model was similar in both cohorts, with a C statistic above 0.70, with good calibration of observed and predicted risks. The new prediction model that has been developed and validated with clinical measurements that are available at the point of initiation of PD and could serve as a tool to screen for patients at high risk of cardiovascular death and tailor more intensive cardio-protective care.
Oxidative C-H activation of amines using protuberant lychee-like goethite
Authors: Verma Sanny , Baig R. B. Nasir , Nadagouda Mallikarjuna N. , Varma Rajender S. 
Published: January 2018

AbstractGoethite with protuberant lychee morphology has been synthesized that accomplishes C-H activation of N-methylanilines to generate α-aminonitriles; the catalyst takes oxygen from air and uses it as a co-oxidant in the process.
High-throughput sequencing analysis revealed the regulation patterns of small RNAs on the development of A. comosus var. bracteatus leaves
Authors: Xiong Ying-Yuan , Ma Jun , He Ye-Hua , Lin Zhen , Li Xia , Yu San-Miao , Li Rui-Xue , Jiang Fu-Xing , Li Xi , Huang Zhuo , Sun Ling-Xia 
Published: January 2018

AbstractStudies of the molecular mechanisms involved in the formation of the albino leaf cells are important for understanding the development of chimera leaves in Ananas comosus var. bracteatus. In this study, we identified a total of 163 novel miRNAs involved in the development of complete white (CWh) and complete green (CGr) leaves using high-throughput sequencing method. The potential miRNA target genes were predicted and annotated using the NR, Swiss-Prot, GO, COG, KEGG, KOG and Pfam databases. The main biological processes regulated by miRNAs were revealed. The miRNAs which potentially play important roles in the development of the leaves and the albino of the CWh leaf cells were selected and their expression patterns were analyzed. The expression levels of nine miRNAs and their potential target genes were studied using qRT-PCR. These results will help to elucidate the functional and regulatory roles of miRNAs in the formation of the albino cells and the development of the leaves of A. comosus var. bracteatus. These data may also be helpful as a resource for studies of small RNA in other leaf color chimeric plant species.
Magneto-optical detection of spin accumulation under the influence of mechanical rotation
Authors: Hirohata Atsufumi , Baba Yuji , Murphy Benedict A. , Ng Benny , Yao Yunqi , Nagao Kazuki , Kim Jun-young 
Published: January 2018

AbstractThe generation of spin-polarised carriers in a non-magnetic material holds the key to realise highly efficient spintronic devices. Recently, it has been shown that the large spin-orbit coupling can generate spin-polarised currents in noble metals such as tungsten and platinum. Especially, if small samples of such metals are rotated on a plane disc in the presence of a perpendicular magnetic field, the orbital angular momentum is altered leading to a segregation of spin up and spin down electrons, i.e., a spin current in the samples. This is manifested via an induced magnetic moment on the metal. In this letter, magneto-optical Kerr effect (MOKE) is used to detect induced magnetic moments which allows remote measurements on metal samples rotating at 100~210 Hz. Our results confirm the mechanical generation of spin-polarised currents via optical detection of spin accumulation.
The intrinsically disordered Tarp protein from chlamydia binds actin with a partially preformed helix
Authors: Tolchard James , Walpole Samuel J. , Miles Andrew J. , Maytum Robin , Eaglen Lawrence A. , Hackstadt Ted , Wallace B. A. , Blumenschein Tharin M. A. 
Published: January 2018

AbstractTarp (translocated actin recruiting phosphoprotein) is an effector protein common to all chlamydial species that functions to remodel the host-actin cytoskeleton during the initial stage of infection. In C. trachomatis, direct binding to actin monomers has been broadly mapped to a 100-residue region (726–825) which is predicted to be predominantly disordered, with the exception of a ~10-residue α-helical patch homologous to other WH2 actin-binding motifs. Biophysical investigations demonstrate that a Tarp726–825 construct behaves as a typical intrinsically disordered protein; within it, NMR relaxation measurements and chemical shift analysis identify the ten residue WH2-homologous region to exhibit partial α-helix formation. Isothermal titration calorimetry experiments on the same construct in the presence of monomeric G-actin show a well defined binding event with a 1:1 stoichiometry and Kd of 102 nM, whilst synchrotron radiation circular dichroism spectroscopy suggests the binding is concomitant with an increase in helical secondary structure. Furthermore, NMR experiments in the presence of G-actin indicate this interaction affects the proposed WH2-like α-helical region, supporting results from in silico docking calculations which suggest that, when folded, this α-helix binds within the actin hydrophobic cleft as seen for other actin-associated proteins.
Predator arrival elicits differential dispersal, change in age structure and reproductive performance in a prey population
Authors: Payo-Payo A. , Sanz-Aguilar A. , Genovart M. , Bertolero A. , Piccardo J. , Camps D. , Ruiz-Olmo J. , Oro D. 
Published: January 2018

AbstractPredators are an important ecological and evolutionary force shaping prey population dynamics. Ecologists have extensively assessed the lethal effects of invasive predators on prey populations. However, the role of non-lethal effects, such as physiological stress or behavioural responses like dispersal, has been comparatively overlooked and their potential population effects remain obscure. Over the last 23 years, we developed a mark-recapture program for the Audouin’s gull and an intensive carnivore monitoring program to assess how the appearance and invasion of the study site by carnivores affects population dynamics. We evaluate changes in turnover of discrete breeding patches within the colony, age structure and breeding performance. Once carnivores entered the colony, the number of occupied patches increased, indicating a higher patch turnover. Breeders responded by moving to areas less accessible to carnivores. More importantly, the presence of carnivores caused differential (and density-independent) breeding dispersal: experienced, better-performing breeders were more likely to leave the colony than younger breeders. This differential dispersal modified the age structure and reduced the reproductive performance of the population. Our results confirm the importance experience in the study of populations. The role of differential dispersal for animal population dynamics might be more important than previously thought, especially under scenarios of global change.
Metallic phase in stoichiometric CeOBiS2 revealed by space-resolved ARPES
Authors: Sugimoto T. , Paris E. , Wakita T. , Terashima K. , Yokoya T. , Barinov A. , Kajitani J. , Higashinaka R. , Matsuda T. D. , Aoki Y. , Mizokawa T. , Saini N. L. 
Published: January 2018

AbstractRecently CeOBiS2 system without any fluorine doping is found to show superconductivity posing question on its origin. Using space resolved ARPES we have found a metallic phase embedded in the morphological defects and at the sample edges of stoichiometric CeOBiS2. While bulk of the sample is semiconducting, the embedded metallic phase is characterized by the usual electron pocket at X point, similar to the Fermi surface of doped BiS2-based superconductors. Typical size of the observed metallic domain is larger than the superconducting correlation length of the system suggesting that the observed superconductivity in undoped CeOBiS2 might be due to this embedded metallic phase at the defects. The results also suggest a possible way to develop new systems by manipulation of the defects in these chalcogenides with structural instability.
Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound
Authors: Islam Md. Koushikul , Strand Mårten , Saleeb Michael , Svensson Richard , Baranczewski Pawel , Artursson Per , Wadell Göran , Ahlm Clas , Elofsson Mikael , Evander Magnus 
Published: January 2018

AbstractRift Valley fever virus (RVFV) is a mosquito-borne hemorrhagic fever virus affecting both humans and animals with severe morbidity and mortality and is classified as a potential bioterror agent due to the possible aerosol transmission. At present there is no human vaccine or antiviral therapy available. Thus, there is a great need to develop new antivirals for treatment of RVFV infections. Benzavir-2 was previously identified as potent inhibitor of human adenovirus, herpes simplex virus type 1, and type 2. Here we assess the anti-RVFV activity of benzavir-2 together with four structural analogs and determine pre-clinical pharmacokinetic parameters of benzavir-2. In vitro, benzavir-2 efficiently inhibited RVFV infection, viral RNA production and production of progeny viruses. In vitro, benzavir-2 displayed satisfactory solubility, good permeability and metabolic stability. In mice, benzavir-2 displayed oral bioavailability with adequate maximum serum concentration. Oral administration of benzavir-2 formulated in peanut butter pellets gave high systemic exposure without any observed toxicity in mice. To summarize, our data demonstrated potent anti-RVFV activity of benzavir-2 in vitro together with a promising pre-clinical pharmacokinetic profile. This data support further exploration of the antiviral activity of benzavir-2 in in vivo efficacy models that may lead to further drug development for human use.