WGE: a CRISPR database for genome engineering

WGE:CRISPR数据库基因组工程

Summary: The rapid development of CRISPR-Cas9 mediated genome editing techniques has given rise to a number of online and stand-alone tools to find and score CRISPR sites for whole genomes. Here we describe the Wellcome Trust Sanger Institute Genome Editing database (WGE), which uses novel methods to compute, visualize and select optimal CRISPR sites in a genome browser environment. The WGE database currently stores single and paired CRISPR sites and pre-calculated off-target information for CRISPRs located in the mouse and human exomes. Scoring and display of off-target sites is simple, and intuitive, and filters can be applied to identify high-quality CRISPR sites rapidly. WGE also provides a tool for the design and display of gene targeting vectors in the same genome browser, along with gene models, protein translation and variation tracks. WGE is open, extensible and can be set up to compute and present CRISPR sites for any genome.

Availability and implementation: The WGE database is freely available at www.sanger.ac.uk/htgt/wge

Contact: vvi@sanger.ac.uk or skarnes@sanger.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

GLASS: a comprehensive database for experimentally validated GPCR-ligand associations

玻璃:一个全面的数据库通过实验验证GPCR-ligand关联

Motivation: G protein-coupled receptors (GPCRs) are probably the most attractive drug target membrane proteins, which constitute nearly half of drug targets in the contemporary drug discovery industry. While the majority of drug discovery studies employ existing GPCR and ligand interactions to identify new compounds, there remains a shortage of specific databases with precisely annotated GPCR-ligand associations.

Results: We have developed a new database, GLASS, which aims to provide a comprehensive, manually curated resource for experimentally validated GPCR-ligand associations. A new text-mining algorithm was proposed to collect GPCR-ligand interactions from the biomedical literature, which is then crosschecked with five primary pharmacological datasets, to enhance the coverage and accuracy of GPCR-ligand association data identifications. A special architecture has been designed to allow users for making homologous ligand search with flexible bioactivity parameters. The current database contains ~500 000 unique entries, of which the vast majority stems from ligand associations with rhodopsin- and secretin-like receptors. The GLASS database should find its most useful application in various in silico GPCR screening and functional annotation studies.

Availability and implementation: The website of GLASS database is freely available at http://zhanglab.ccmb.med.umich.edu/GLASS/.

Contact: zhng@umich.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • DATABASES AND ONTOLOGIES

Fast parametric time warping of peak lists

快速参数时间扭曲的峰值列表

Summary: Alignment of peaks across samples is a difficult but unavoidable step in the data analysis for all analytical techniques containing a separation step like chromatography. Important application examples are the fields of metabolomics and proteomics. Parametric time warping (PTW) has already shown to be very useful in these fields because of the highly restricted form of the warping functions, avoiding overfitting. Here, we describe a new formulation of PTW, working on peak-picked features rather than on complete profiles. Not only does this allow for a much more smooth integration in existing pipelines, it also speeds up the (already among the fastest) algorithm by orders of magnitude. Using two publicly available datasets we show the potential of the new approach. The first set is a LC–DAD dataset of grape samples, and the second an LC–MS dataset of apple extracts.

Availability and implementation: Parametric time warping of peak lists is implemented in the ptw package, version 1.9.1 and onwards, available from Github (https://github.com/rwehrens/ptw) and CRAN (http://cran.r-project.org). The package also contains a vignette, providing more theoretical details and scripts to reproduce the results below.

Contact: ron.wehrens@wur.nl

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

BFC: correcting Illumina sequencing errors

佛:纠正Illumina公司测序错误

Summary: BFC is a free, fast and easy-to-use sequencing error corrector designed for Illumina short reads. It uses a non-greedy algorithm but still maintains a speed comparable to implementations based on greedy methods. In evaluations on real data, BFC appears to correct more errors with fewer overcorrections in comparison to existing tools. It particularly does well in suppressing systematic sequencing errors, which helps to improve the base accuracy of de novo assemblies.

Availability and implementation: https://github.com/lh3/bfc

Contact: hengli@broadinstitute.org

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

PsyGeNET: a knowledge platform on psychiatric disorders and their genes

PsyGeNET:精神障碍和他们的基因知识的平台

Summary: PsyGeNET (Psychiatric disorders and Genes association NETwork) is a knowledge platform for the exploratory analysis of psychiatric diseases and their associated genes. PsyGeNET is composed of a database and a web interface supporting data search, visualization, filtering and sharing. PsyGeNET integrates information from DisGeNET and data extracted from the literature by text mining, which has been curated by domain experts. It currently contains 2642 associations between 1271 genes and 37 psychiatric disease concepts. In its first release, PsyGeNET is focused on three psychiatric disorders: major depression, alcohol and cocaine use disorders. PsyGeNET represents a comprehensive, open access resource for the analysis of the molecular mechanisms underpinning psychiatric disorders and their comorbidities.

Availability and implementation: The PysGeNET platform is freely available at http://www.psyge net.org/. The PsyGeNET database is made available under the Open Database License (http://open datacommons.org/licenses/odbl/1.0/).

Contact: lfurlong@imim.es

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

GOplot: an R package for visually combining expression data with functional analysis

GOplot:R包视觉表达数据与功能分析相结合

Summary: Despite the plethora of methods available for the functional analysis of omics data, obtaining comprehensive-yet detailed understanding of the results remains challenging. This is mainly due to the lack of publicly available tools for the visualization of this type of information. Here we present an R package called GOplot, based on ggplot2, for enhanced graphical representation. Our package takes the output of any general enrichment analysis and generates plots at different levels of detail: from a general overview to identify the most enriched categories (bar plot, bubble plot) to a more detailed view displaying different types of information for molecules in a given set of categories (circle plot, chord plot, cluster plot). The package provides a deeper insight into omics data and allows scientists to generate insightful plots with only a few lines of code to easily communicate the findings.

Availability and Implementation: The R package GOplot is available via CRAN-The Comprehensive R Archive Network: http://cran.r-project.org/web/packages/GOplot. The shiny web application of the Venn diagram can be found at: https://wwalter.shinyapps.io/Venn/. A detailed manual of the package with sample figures can be found at https://wencke.github.io/

Contact: fscabo@cnic.es or mricote@cnic.es

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

Tax4Fun: predicting functional profiles from metagenomic 16S rRNA data

Tax4Fun:预测功能从metagenomic 16 s rRNA的数据资料

Motivation: The characterization of phylogenetic and functional diversity is a key element in the analysis of microbial communities. Amplicon-based sequencing of marker genes, such as 16S rRNA, is a powerful tool for assessing and comparing the structure of microbial communities at a high phylogenetic resolution. Because 16S rRNA sequencing is more cost-effective than whole metagenome shotgun sequencing, marker gene analysis is frequently used for broad studies that involve a large number of different samples. However, in comparison to shotgun sequencing approaches, insights into the functional capabilities of the community get lost when restricting the analysis to taxonomic assignment of 16S rRNA data.

Results: Tax4Fun is a software package that predicts the functional capabilities of microbial communities based on 16S rRNA datasets. We evaluated Tax4Fun on a range of paired metagenome/16S rRNA datasets to assess its performance. Our results indicate that Tax4Fun provides a good approximation to functional profiles obtained from metagenomic shotgun sequencing approaches.

Availability and implementation: Tax4Fun is an open-source R package and applicable to output as obtained from the SILVAngs web server or the application of QIIME with a SILVA database extension. Tax4Fun is freely available for download at http://tax4fun.gobics.de/.

Contact: kasshau@gwdg.de

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • APPLICATIONS NOTE

The SwissLipids knowledgebase for lipid biology

脂类生物的SwissLipids知识库

Motivation: Lipids are a large and diverse group of biological molecules with roles in membrane formation, energy storage and signaling. Cellular lipidomes may contain tens of thousands of structures, a staggering degree of complexity whose significance is not yet fully understood. High-throughput mass spectrometry-based platforms provide a means to study this complexity, but the interpretation of lipidomic data and its integration with prior knowledge of lipid biology suffers from a lack of appropriate tools to manage the data and extract knowledge from it.

Results: To facilitate the description and exploration of lipidomic data and its integration with prior biological knowledge, we have developed a knowledge resource for lipids and their biology—SwissLipids. SwissLipids provides curated knowledge of lipid structures and metabolism which is used to generate an in silico library of feasible lipid structures. These are arranged in a hierarchical classification that links mass spectrometry analytical outputs to all possible lipid structures, metabolic reactions and enzymes. SwissLipids provides a reference namespace for lipidomic data publication, data exploration and hypothesis generation. The current version of SwissLipids includes over 244 000 known and theoretically possible lipid structures, over 800 proteins, and curated links to published knowledge from over 620 peer-reviewed publications. We are continually updating the SwissLipids hierarchy with new lipid categories and new expert curated knowledge.

Availability: SwissLipids is freely available at http://www.swisslipids.org/.

Contact: alan.bridge@isb-sib.ch

Supplementary information: Supplementary data are available at Bioinformatics online.

[详细]

  • Bioinformatics
  • 10年前
  • ORIGINAL PAPER

Applications of the CRISPR–Cas9 system in cancer biology

–的CRISPR Cas9系统在肿瘤生物学中的应用

The prokaryotic type II CRISPR–Cas9 (clustered regularly interspaced short palindromic repeats–CRISPR-associated 9) system is rapidly revolutionizing the field of genetic engineering, allowing researchers to alter the genomes of a large range of organisms with relative ease. Experimental approaches based on this versatile technology have the

[详细]

  • Nature Reviews Cancer 15, 387 (2015)
  • 10年前
  • Progress

Single prokaryotic cell isolation and total transcript amplification protocol for transcriptomic analysis

单核细胞分离和全转录扩增转录组分析

This protocol enables amplification of the total transcript of a single prokaryotic cell for in-depth analysis. Laser-capture microdissection is used to isolate single cells, and amplified cDNA can be further analyzed by microarray.

[详细]

  • Nature Protocols 10, 974 (2015)
  • 10年前
  • Protocol

Exploring RNA polymerase regulation by NMR spectroscopy

通过核磁共振光谱探索RNA聚合酶调控

RNA synthesis is a central process in all organisms, with RNA polymerase (RNAP) as the key enzyme. Multisubunit RNAPs are evolutionary related and are tightly regulated by a multitude of transcription factors. Although Escherichia coli RNAP has been studied extensively, only little information is available about its dynamics and transient interactions. This information, however, are crucial for the complete understanding of transcription regulation in atomic detail. To study RNAP by NMR spectroscopy we developed a highly efficient procedure for the assembly of active RNAP from separately expressed subunits that allows specific labeling of the individual constituents. We recorded [1H,13C] correlation spectra of isoleucine, leucine, and valine methyl groups of complete RNAP and the separately labeled β’ subunit within reconstituted RNAP. We further produced all RNAP subunits individually, established experiments to determine which RNAP subunit a certain regulator binds to, and identified the β subunit to bind NusE.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Adaptive Spontaneous Transitions between Two Mechanisms of Numerical Averaging

自适应自发跃迁机制两者之间的数值平均

We investigated the mechanism with which humans estimate numerical averages. Participants were presented with 4, 8 or 16 (two-digit) numbers, serially and rapidly (2 numerals/second) and were instructed to convey the sequence average. As predicted by a dual, but not a single-component account, we found a non-monotonic influence of set-size on accuracy. Moreover, we observed a marked decrease in RT as set-size increases and RT-accuracy tradeoff in the 4-, but not in the 16-number condition. These results indicate that in accordance with the normative directive, participants spontaneously employ analytic/sequential thinking in the 4-number condition and intuitive/holistic thinking in the 16-number condition. When the presentation rate is extreme (10 items/sec) we find that, while performance still remains high, the estimations are now based on intuitive processing. The results are accounted for by a computational model postulating population-coding underlying intuitive-averaging and working-memory-mediated symbolic procedures underlying analytical-averaging, with flexible allocation between the two.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

A new arylbenzofuran derivative functions as an anti-tumour agent by inducing DNA damage and inhibiting PARP activity

一种新的芳基苯并呋喃类衍生物作为抗肿瘤剂诱导的DNA损伤和抑制PARP活性

We previously reported that 7-hydroxy-5, 4’-dimethoxy-2-arylbenzofuran (HDAB) purified from Livistona chinensis is a key active agent. The present study investigated the function and molecular mechanism of HDAB. HDAB treatment of cervical cancer cells resulted in S phase arrest and apoptosis, together with cyclin A2 and CDK2 upregulation. Cyclin A2 siRNA and a CDK inhibitor efficiently relieved S phase arrest but increased the apoptosis rate. Mechanistic studies revealed that HDAB treatment significantly increased DNA strand breaks in an alkaline comet assay and induced ATM, CHK1, CHK2 and H2A.X phosphorylation. Wortmannin (a broad inhibitor of PIKKs) and CGK733 (a specific ATM inhibitor), but not LY294002 (a phosphatidylinositol 3-kinase inhibitor) or NU7026 (a DNA-PK specific inhibitor), prevented H2A.X phosphorylation and γH2A.X-positive foci formation in the nuclei, reversed S phase arrest and promoted the HDAB-induced apoptosis, suggesting that HDAB is a DNA damaging agent that can activate the ATM-dependent DNA repair response, thereby contributing to cell cycle arrest. In addition, molecular docking and in vitro activity assays revealed that HDAB can correctly dock into the hydrophobic pocket of PARP-1 and suppress PARP-1 ADP-ribosylation activity. Thus, the results indicated that HDAB can function as an anti-cancer agent by inducing DNA damage and inhibiting PARP activity.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

A Biologically Inspired Network Design Model

一个受生物启发的网络设计模型

A network design problem is to select a subset of links in a transport network that satisfy passengers or cargo transportation demands while minimizing the overall costs of the transportation. We propose a mathematical model of the foraging behaviour of slime mould P. polycephalum to solve the network design problem and construct optimal transport networks. In our algorithm, a traffic flow between any two cities is estimated using a gravity model. The flow is imitated by the model of the slime mould. The algorithm model converges to a steady state, which represents a solution of the problem. We validate our approach on examples of major transport networks in Mexico and China. By comparing networks developed in our approach with the man-made highways, networks developed by the slime mould, and a cellular automata model inspired by slime mould, we demonstrate the flexibility and efficiency of our approach.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Networks: On the relation of bi- and multivariate measures

网络:在双的关系和多元的措施

A reliable inference of networks from observations of the nodes’ dynamics is a major challenge in physics. Interdependence measures such as a the correlation coefficient or more advanced methods based on, e.g., analytic phases of signals are employed. For several of these interdependence measures, multivariate counterparts exist that promise to enable distinguishing direct and indirect connections. Here, we demonstrate analytically how bivariate measures relate to the respective multivariate ones; this knowledge will in turn be used to demonstrate the implications of thresholded bivariate measures for network inference. Particularly, we show, that random networks are falsely identified as small-world networks if observations thereof are treated by bivariate methods. We will employ the correlation coefficient as an example for such an interdependence measure. The results can be readily transferred to all interdependence measures partializing for information of thirds in their multivariate counterparts.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Evolutionary food web model based on body masses gives realistic networks with permanent species turnover

根据体质量进化的食物网模型给出了现实网络的永久性物种周转

The networks of predator-prey interactions in ecological systems are remarkably complex, but nevertheless surprisingly stable in terms of long term persistence of the system as a whole. In order to understand the mechanism driving the complexity and stability of such food webs, we developed an eco-evolutionary model in which new species emerge as modifications of existing ones and dynamic ecological interactions determine which species are viable. The food-web structure thereby emerges from the dynamical interplay between speciation and trophic interactions. The proposed model is less abstract than earlier evolutionary food web models in the sense that all three evolving traits have a clear biological meaning, namely the average body mass of the individuals, the preferred prey body mass, and the width of their potential prey body mass spectrum. We observed networks with a wide range of sizes and structures and high similarity to natural food webs. The model networks exhibit a continuous species turnover, but massive extinction waves that affect more than 50% of the network are not observed.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair

着色性干皮病C组蛋白调节DNA损伤识别的核苷酸切除修复中的SUMO化修饰

The xeroderma pigmentosum group C (XPC) protein complex is a key factor that detects DNA damage and initiates nucleotide excision repair (NER) in mammalian cells. Although biochemical and structural studies have elucidated the interaction of XPC with damaged DNA, the mechanism of its regulation in vivo remains to be understood in more details. Here, we show that the XPC protein undergoes modification by small ubiquitin-related modifier (SUMO) proteins and the lack of this modification compromises the repair of UV-induced DNA photolesions. In the absence of SUMOylation, XPC is normally recruited to the sites with photolesions, but then immobilized profoundly by the UV-damaged DNA-binding protein (UV-DDB) complex. Since the absence of UV-DDB alleviates the NER defect caused by impaired SUMOylation of XPC, we propose that this modification is critical for functional interactions of XPC with UV-DDB, which facilitate the efficient damage handover between the two damage recognition factors and subsequent initiation of NER.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Inferring the connectivity of coupled oscillators from time-series statistical similarity analysis

推断耦合振子的连接从时间序列的统计相似性分析

A system composed by interacting dynamical elements can be represented by a network, where the nodes represent the elements that constitute the system, and the links account for their interactions, which arise due to a variety of mechanisms, and which are often unknown. A popular method for inferring the system connectivity (i.e., the set of links among pairs of nodes) is by performing a statistical similarity analysis of the time-series collected from the dynamics of the nodes. Here, by considering two systems of coupled oscillators (Kuramoto phase oscillators and Rössler chaotic electronic oscillators) with known and controllable coupling conditions, we aim at testing the performance of this inference method, by using linear and non linear statistical similarity measures. We find that, under adequate conditions, the network links can be perfectly inferred, i.e., no mistakes are made regarding the presence or absence of links. These conditions for perfect inference require: i) an appropriated choice of the observed variable to be analysed, ii) an appropriated interaction strength, and iii) an adequate thresholding of the similarity matrix. For the dynamical units considered here we find that the linear statistical similarity measure performs, in general, better than the non-linear ones.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Expanding the chemical space for natural products by Aspergillus-Streptomyces co-cultivation and biotransformation

扩大化学空间天然产物曲霉链霉菌共培养转化

Actinomycetes and filamentous fungi produce a wide range of bioactive compounds, with applications as antimicrobials, anticancer agents or agrochemicals. Their genomes contain a far larger number of gene clusters for natural products than originally anticipated, and novel approaches are required to exploit this potential reservoir of new drugs. Here, we show that co-cultivation of the filamentous model microbes Streptomyces coelicolor and Aspergillus niger has a major impact on their secondary metabolism. NMR-based metabolomics combined with multivariate data analysis revealed several compounds that correlated specifically to co-cultures, including the cyclic dipeptide cyclo(Phe-Phe) and 2-hydroxyphenylacetic acid, both of which were produced by A. niger in response to S. coelicolor. Furthermore, biotransformation studies with o-coumaric acid and caffeic acid resulted in the production of the novel compounds (E)-2-(3-hydroxyprop-1-en-1-yl)-phenol and (2E,4E)-3-(2-carboxy-1-hydroxyethyl)-2,4-hexadienedioxic acid, respectively. This highlights the utility of microbial co-cultivation combined with NMR-based metabolomics as an efficient pipeline for the discovery of novel natural products.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Transcriptional responses of invasive and indigenous whiteflies to different host plants reveal their disparate capacity of adaptation

侵袭性与土著烟粉虱对不同寄主植物的适应能力,揭示其不同的转录反应

The whitefly Bemisia tabaci contains more than 35 cryptic species. The higher adaptability of Middle East-Asia Minor 1 (MEAM1) cryptic species has been recognized as one important factor for its invasion and displacement of other indigenous species worldwide. Here we compared the performance of the invasive MEAM1 and the indigenous Asia II 3 whitefly species following host plant transfer from a suitable host (cotton) to an unsuitable host (tobacco) and analyzed their transcriptional responses. After transfer to tobacco for 24 h, MEAM1 performed much better than Asia II 3. Transcriptional analysis showed that the patterns of gene regulation were very different with most of the genes up-regulated in MEAM1 but down-regulated in Asia II 3. Whereas carbohydrate and energy metabolisms were repressed in Asia II 3, the gene expression and protein metabolisms were activated in MEAM1. Compared to the constitutive high expression of detoxification genes in MEAM1, most of the detoxification genes were down-regulated in Asia II 3. Enzymatic activities of P450, GST and esterase further verified that the detoxification of MEAM1 was much higher than that of Asia II 3. These results reveal obvious differences in responses of MEAM1 and Asia II 3 to host transfer.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Crystal structure of TRIM20 C-terminal coiled-coil/B30.2 fragment: implications for the recognition of higher order oligomers

trim20晶体结构的C-末端卷曲/ B30.2片段:对于高阶低聚物的识别的影响

Many tripartite motif-containing (TRIM) proteins, comprising RING-finger, B-Box, and coiled-coil domains, carry additional B30.2 domains on the C-terminus of the TRIM motif and are considered to be pattern recognition receptors involved in the detection of higher order oligomers (e.g. viral capsid proteins). To investigate the spatial architecture of domains in TRIM proteins we determined the crystal structure of the TRIM20Δ413 fragment at 2.4 Å resolution. This structure comprises the central helical scaffold (CHS) and C-terminal B30.2 domains and reveals an anti-parallel arrangement of CHS domains placing the B-box domains 170 Å apart from each other. Small-angle X-ray scattering confirmed that the linker between CHS and B30.2 domains is flexible in solution. The crystal structure suggests an interaction between the B30.2 domain and an extended stretch in the CHS domain, which involves residues that are mutated in the inherited disease Familial Mediterranean Fever. Dimerization of B30.2 domains by means of the CHS domain is crucial for TRIM20 to bind pro-IL-1β in vitro. To exemplify how TRIM proteins could be involved in binding higher order oligomers we discuss three possible models for the TRIM5α/HIV-1 capsid interaction assuming different conformations of B30.2 domains.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Discovery and characterization of novel small-molecule inhibitors targeting nicotinamide phosphoribosyltransferase

发现和新靶点的小分子抑制剂烟酰胺磷酸核糖转移酶的特性

Nicotinamide phosphoribosyltransferase (NAMPT) is a promising anticancer target. Using high throughput screening system targeting NAMPT, we obtained a potent NAMPT inhibitor MS0 (China Patent ZL201110447488.9) with excellent in vitro activity (IC50 = 9.87 ± 1.15nM) and anti-proliferative activity against multiple human cancer cell lines including stem-like cancer cells. Structure-activity relationship studies yielded several highly effective analogues. These inhibitors specifically bound NAMPT, rather than downstream NMNAT. We provided the first chemical case using cellular thermal shift assay to explain the difference between in vitro and cellular activity; MS7 showed best in vitro activity (IC50 = 0.93 ± 0.29 nM) but worst cellular activity due to poor target engagement in living cells. Site-directed mutagenesis studies identified important residues for NAMPT catalytic activity and inhibitor binding. The present findings contribute to deep understanding the action mode of NAMPT inhibitors and future development of NAMPT inhibitors as anticancer agents.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Understanding the association of Escherichia coli with diverse macroalgae in the lagoon of Venice

了解在威尼斯泻湖不同海藻大肠埃希菌协会

Recent studies provided evidence that the macroalga Cladopohora in lakes hosts associated Escherichia coli, with consequences on the environmental and human health. We expanded these investigations to other macroalgae (Ulva spp., Sargassum muticum and Undaria pinnatifida) widespread in the lagoon of Venice (Italy). Attached E. coli were abundant, accounting up to 3,250 CFU gram−1 of alga. Macroalgal-associated isolates belonged to all E. coli phylogroups, including pathogenic ones, and to Escherichia cryptic clades. Attached E. coli showed potential to grow even at in situ temperature on macroalgal extracts as only source of carbon and nutrients, and ability to produce biofilm in vitro. The genotypic diversity of the attached isolates was high, with significant differences between algae and the overlying water. Our evidences suggest that attached populations consist of both resident and transient strains, likely resulting from the heterogeneous input of fecal bacteria from the city. We report that cosmopolitan and invasive macroalgae may serve as source of E. coli, including pathogenic genotypes, and that this habitat can potentially support their growth. Considering the global diffusion of the macroalgae here studied, this phenomenon is likely occurring in other coastal cities worldwide and deserves further investigations from either the sanitary and ecological perspectives.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article

Induction chemotherapy with concurrent chemoradiotherapy versus concurrent chemoradiotherapy for locally advanced squamous cell carcinoma of head and neck: a meta-analysis

对于局部晚期头颈部鳞状细胞癌同步放化疗与同步放化疗诱导化疗的荟萃分析

Concurrent chemoradiotherapy (CCRT) has been considered to be the standard of care for locally advanced squamous cell carcinoma of head and neck (LA-SCCHN). Whether induction chemotherapy (IC) with CCRT will further improve the clinical outcomes or not is still unclear. We conducted a meta-analysis to compare the two regimens for LA-SCCHN. Literature searches were carried out in PubMed, Embase, Cochrane Library and Chinese Biology Medicine from inception to November 2014. Five prospective randomized controlled trials (RCTs) with 922 patients were included in meta-analysis. Results were expressed as hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs). Compared with CCRT, IC with CCRT showed no statistically significant differences in overall survival (OS), progression-free survival (PFS), overall response rate (ORR) or locoregional recurrence rate (LRR), but could increase risks of grade 3–4 febrile neutropenia (P = 0.0009) and leukopenia (P = 0.04). In contrast, distant metastasis rate (DMR) decreased (P = 0.006) and complete response rate (CR) improved (P = 0.010) for IC with CCRT. In conclusion, the current studies do not support the use of IC with CCRT over CCRT, and the further positioning of IC with CCRT as standard treatment for LA-SCCHN will come from more RCTs directly comparing IC followed by CCRT with CCRT.

[详细]

  • Scientific Reports 5
  • 10年前
  • Article