scholarly journals An atlas of the binding specificities of transcription factors in Pseudomonas aeruginosa directs prediction of novel regulators in virulence

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Tingting Wang ◽  
Wenju Sun ◽  
Ligang Fan ◽  
Canfeng Hua ◽  
Nan Wu ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Gene Body ◽  
Sequence Motifs ◽  
Prevention Strategies ◽  
Future Studies ◽  
Treatment And Prevention ◽  
Body Regions ◽  
Intergenic Regions ◽  
Systematic Evolution ◽  
Exponential Enrichment

A high-throughput systematic evolution of ligands by exponential enrichment assay was applied to 371 putative TFs in P. aeruginosa, which resulted in the robust enrichment of 199 sequence motifs describing the binding specificities of 182 TFs. By scanning the genome, we predicted in total 33,709 significant interactions between TFs and their target loci, which were more than 11-fold enriched in the intergenic regions but depleted in the gene body regions. To further explore and delineate the physiological and pathogenic roles of TFs in P. aeruginosa, we constructed regulatory networks for nine major virulence-associated pathways, and found that 51 TFs were potentially significantly associated with these virulence pathways, 32 of which had not been characterized before, and some were even involved in multiple pathways. These results will significantly facilitate future studies on transcriptional regulation in P. aeruginosa and other relevant pathogens, and accelerate to discover effective treatment and prevention strategies for the associated infectious diseases.

APTANI2: update of aptamer selection through sequence-structure analysis

2019 ◽  
Vol 36 (7) ◽  
pp. 2266-2268 ◽  
Author(s):  
Jimmy Caroli ◽  
Mattia Forcato ◽  
Silvio Bicciato
Keyword(s):  
Structure Analysis ◽  
Graphical User Interface ◽  
Source Code ◽  
Supplementary Information ◽  
Sequence Motifs ◽  
Computational Tool ◽  
Sequence Structure ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Aptamer Sequence

Abstract Summary Here we present APTANI2, an expanded and optimized version of APTANI, a computational tool for selecting target-specific aptamers from high-throughput-Systematic Evolution of Ligands by Exponential Enrichment data through sequence-structure analysis. As compared to its original implementation, APTANI2 ranks aptamers and identifies relevant structural motifs through the calculation of a score that combines frequency and structural stability of each secondary structure predicted in any aptamer sequence. In addition, APTANI2 comprises modules for a deeper investigation of sequence motifs and secondary structures, a graphical user interface that enhances its usability, and coding solutions that improve performances. Availability and implementation Source code, documentation and example command lines can be downloaded from http://aptani.unimore.it. APTANI2 is implemented in Python 3.4, released under the GNU GPL3.0 License, and compatible with Linux, Mac OS and the MS Windows subsystem for Linux. Supplementary information Supplementary information is available at Bioinformatics online

FEATURES OF ORGANOPHOSPHATES IMMOBILIZATION VIA STREPTAVIDIN-BIOTIN SYSTEM FOR EXPERIMENTS ON SELECTION OF APTAMERS

2020 ◽  
pp. 12-20
Author(s):  
D. A. Belinskaya ◽  
Yu. V. Chelusnova ◽  
V. V. Abzianidze ◽  
N. V. Goncharov
Keyword(s):  
Polyethylene Glycol ◽  
Organophosphorus Compounds ◽  
Binding Energies ◽  
Rna Aptamers ◽  
Main Method ◽  
Modeling Methods ◽  
Molecular Dynamics Methods ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Selection Of

Poisoning with organophosphorus compounds occupy one of the leading places in exotoxicosis. At the first stage, the detoxification of organophosphates can be provided with the help of DNA or RNA aptamers that bind the poison in the bloodstream. Currently, the main method of searching for aptamers is the experimental method of systematic evolution of ligands by exponential enrichment (SELEX). In the process of aptamer selection, the target molecule must be immobilized via the streptavidin-biotin complex. Since the poison molecule is small in size, to increase its availability for binding to aptamer, it is necessary to use a spacer between organophosphorus compounds and biotin. The aim of this work was to optimize the selection of aptamers for organophosphorus compounds by increasing the availability of a poison molecule immobilized via the streptavidin-biotin complex on the example of paraoxon. For this purpose, three spacers between organophosphorus compounds and biotin were tested using molecular modeling methods: three links of polyethylene glycol (3-PEG), four links of polyethylene glycol (4-PEG) and aminohexyl. The conformation of the biotinylated paraoxon complex with streptavidin and the interaction of paraoxon with the binding fragment of the aptamer were modeled using molecular docking and molecular dynamics methods. The ability of biotinylated paraoxon to bind to the aptamer has been evaluated by analyzing the surface area of the paraoxon available to the solvent, as well as by calculating the free binding energies. It has been shown that only in the case of aminohexyl immobilized paraoxon can contact the aptamer. At the final stage, the synthesis of paraoxon bound to biotin via aminohexyl was carried out.

scholarly journals Circulating HIV DNA Correlates With Neurocognitive Impairment in Older HIV-infected Adults on Suppressive ART

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Michelli Faria de Oliveira ◽  
Ben Murrell ◽  
Josué Pérez-Santiago ◽  
Milenka Vargas ◽  
Ronald J. Ellis ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Neurocognitive Impairment ◽  
Neurocognitive Functioning ◽  
Neurocognitive Disorder ◽  
Prevention Strategies ◽  
Hiv Dna ◽  
Treatment And Prevention ◽  
Markers Of Inflammation ◽  
Underlying Mechanisms ◽  
Dna Reservoir

Abstract Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22–40 years) and 26 older (50–71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels. Among older participants, higher HIV DNA levels were significantly associated with more severe neurocognitive impairment (p = 0.005), particularly in the Executive Functions domain (p = 0.004). No association was observed between HIV DNA and neurocognition among younger individuals. Despite significantly increased inflammation observed in the older group, none of the inflammatory markers were associated with neurocognitive impairment among older HIV+ individuals (p > 0.05). Our study supports the involvement of peripheral HIV DNA reservoir in the pathogenesis of neurocognitive disorder during suppressive ART. Correlates of neurocognitive impairment might differ between younger and older adults, suggesting that future treatment and prevention strategies for HIV-associated neurocognitive disorders likely need to be tailored based on age.

Inhaled therapeutics against TB: The promise of pulmonary treatment and prevention strategies in the clinic

2019 ◽  
pp. 361-375
Author(s):  
Dominique N. Price ◽  
Nitesh K. Kunda ◽  
Elliott K. Miller ◽  
Pavan Muttil
Keyword(s):  
Prevention Strategies ◽  
Treatment And Prevention

scholarly journals The interaction landscape between transcription factors and the nucleosome

2017 ◽  
Author(s):  
Fangjie Zhu ◽  
Lucas Farnung ◽  
Eevi Kaasinen ◽  
Biswajyoti Sahu ◽  
Yimeng Yin ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Affinity Purification ◽  
Rotational Symmetry ◽  
Free Dna ◽  
Nucleosomal Dna ◽  
Direct Gene ◽  
Systematic Evolution ◽  
Modes Of Interaction ◽  
Exponential Enrichment ◽  
Rich Interaction

Nucleosomes cover most of the genome and are thought to be displaced by transcription factors (TFs) in regions that direct gene expression. However, the modes of interaction between TFs and nucleosomal DNA remain largely unknown. Here, we use nucleosome consecutive affinity-purification systematic evolution of ligands by exponential enrichment (NCAP-SELEX) to systematically explore interactions between the nucleosome and 220 TFs representing diverse structural families. Consistently with earlier observations, we find that the vast majority of TFs have less access to nucleosomal DNA than to free DNA. The motifs recovered from TFs bound to nucleosomal and free DNA are generally similar; however, steric hindrance and scaffolding by the nucleosome result in specific positioning and orientation of the motifs. Many TFs preferentially bind close to the end of nucleosomal DNA, or to periodic positions at its solvent-exposed side. TFs often also bind nucleosomal DNA in a particular orientation, because the nucleosome breaks the local rotational symmetry of DNA. Some TFs also specifically interact with DNA located at the dyad position where only one DNA gyre is wound, whereas other TFs prefer sites spanning two DNA gyres and bind specifically to each of them. Our work reveals striking differences in TF binding to free and nucleosomal DNA, and uncovers a rich interaction landscape between the TFs and the nucleosome.

Pattern recognition of enrichment levels of SELEX-based candidate aptamers for human C-reactive protein

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Xinliang Yu ◽  
Ruqin Yu ◽  
Xiaohai Yang
Keyword(s):  
Pattern Recognition ◽  
Latent Variables ◽  
Molecular Descriptors ◽  
Principal Component ◽  
Support Vector ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Systematic Evolution ◽  
Model C ◽  
Exponential Enrichment

AbstractSelecting aptamers for human C-reactive protein (CRP) would be of critical importance in predicting the risk for cardiovascular disease. The enrichment level of DNA aptamers is an important parameter for selecting candidate aptamers for further affinity and specificity determination. This paper is the first report on pattern recognition used for CRP aptamer enrichment levels in the systematic evolution of ligands by exponential enrichment (SELEX) process, by applying structure-activity relationship models. After generating 10 rounds of graphene oxide (GO)-SELEX and 1670 molecular descriptors, eight molecular descriptors were selected and five latent variables were then obtained with principal component analysis (PCA), to develop a support vector classification (SVC) model. The SVC model (C=8.1728 and

Differentiating breast cancer molecular subtypes using a DNA aptamer selected against MCF-7 cells

2018 ◽  
Vol 6 (12) ◽  
pp. 3152-3159 ◽  
Author(s):  
Mei Liu ◽  
Tong Yang ◽  
Zhongsi Chen ◽  
Zhifei Wang ◽  
Nongyue He
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Personalized Therapy ◽  
Dna Aptamer ◽  
Single Stranded Dna ◽  
Systematic Evolution ◽  
Exponential Enrichment ◽  
Mcf 7

Aptamers are single-stranded DNA or RNA oligonucleotides selected by systematic evolution of ligands by exponential enrichment (SELEX), which show great potential in the diagnosis and personalized therapy of cancers, due to their specific advantages over antibodies.

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