scholarly journals Efficient computation of co-transcriptional RNA-ligand interaction dynamics

2018 ◽  
Author(s):  
Michael T. Wolfinger ◽  
Christoph Flamm ◽  
Ivo L. Hofaeker
Keyword(s):  
Gene Expression ◽  
Synthetic Biology ◽  
Efficient Implementation ◽  
Regulatory Rna ◽  
Efficient Computation ◽  
Ligand Interaction ◽  
Interaction Dynamics ◽  
Novel Approach ◽  
First Time ◽  
Metabolite Binding

AbstractRiboswitches form an abundant class of cis-regulatory RNA elements that mediate gene expression by binding a small metabolite. For synthetic biology applications, they are becoming cheap and accessible systems for selectively triggering transcription or translation of downstream genes. Many riboswitches are kinetically controlled, hence knowledge of their co-transcriptional mechanisms is essential. We present here an efficient implementation for analyzing co-transcriptional RNA-ligand interaction dynamics. This approach allows for the first time to model concentration-dependent metabolite binding/unbinding kinetics. We exemplify this novel approach by means of the recently studied I-A 2’-deoxyguanosine (2’dG)-sensing riboswitch from Mesoplasma florum.

scholarly journals Efficient computation of co-transcriptional RNA-ligand interaction dynamics

Methods ◽  
2018 ◽  
Vol 143 ◽  
pp. 70-76 ◽  
Author(s):  
Michael T. Wolfinger ◽  
Christoph Flamm ◽  
Ivo L. Hofacker
Keyword(s):  
Efficient Computation ◽  
Ligand Interaction ◽  
Interaction Dynamics

Gene expression profiling as a novel approach for justifying fixed drug combination products

Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
O Kelber ◽  
H Abdel-Aziz ◽  
SN Okpanyi ◽  
G Ulrich-Merzenich
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Drug Combination ◽  
Expression Profiling ◽  
Novel Approach ◽  
Fixed Drug

Probing the Substrate Promiscuity of Isopentenyl Phosphate Kinase as a Platform for Hemiterpene Analogue Production

2019 ◽  
Author(s):  
Sean Lund ◽  
Taylor Courtney ◽  
Gavin Williams
Keyword(s):  
Synthetic Biology ◽  
Building Blocks ◽  
Isoprenoid Biosynthesis ◽  
Thermoplasma Acidophilum ◽  
Substrate Promiscuity ◽  
Enzymatic Pathways ◽  
First Time ◽  
Rate Limiting ◽  
Alcohol Dependent ◽  
Isopentenyl Phosphate

Isoprenoids are a large class of natural products with wide-ranging applications. Synthetic biology approaches to the manufacture of isoprenoids and their new-to-nature derivatives are limited due to the provision in Nature of just two hemiterpene building blocks for isoprenoid biosynthesis. To address this limitation, artificial chemo-enzymatic pathways such as the alcohol-dependent hemiterpene pathway (ADH) serve to leverage consecutive kinases to convert exogenous alcohols to pyrophosphates that could be coupled to downstream isoprenoid biosynthesis. To be successful, each kinase in this pathway should be permissive of a broad range of substrates. For the first time, we have probed the promiscuity of the second enzyme in the ADH pathway, isopentenyl phosphate kinase from Thermoplasma acidophilum, towards a broad range of acceptor monophosphates. Subsequently, we evaluate the suitability of this enzyme to provide non-natural pyrophosphates and provide a critical first step in characterizing the rate limiting steps in the artificial ADH pathway.<br>

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

scholarly journals Urban temporary housing environments—from a systematic comparison towards an integrated typology

2021 ◽  
Author(s):  
Mirjam Stocker ◽  
Gerda Schneider ◽  
Julia Zeilinger ◽  
Gloria Rose ◽  
Doris Damyanovic ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Housing Demand ◽  
Economic Aspects ◽  
Temporary Housing ◽  
Open Spaces ◽  
Systematic Comparison ◽  
Human Needs ◽  
Novel Approach ◽  
Environmental Events ◽  
First Time

AbstractHousing plays a central role in everyday life and the fulfillment of human needs. Temporary housing demand can occur due to migration, extreme environmental events or personal decisions, and is expected to increase in the upcoming years. This study aims to create a general understanding of temporary housing. We conducted an integrated comparison of 66 international temporary housing examples via tabulation (table work), in an interdisciplinary manner considering details regarding built structure, open spaces, area, infrastructure, organizational and socio-economic aspects. It is the first time that a systematic comparison via tabulation (based on the approach of Braun-Blanquet) is used to classify temporary housing environments. The process is described in detail. The application of the systematic comparison creates a detailed typology that allows extensions and further differentiations. The types that emerge from the tabulation have specific concepts regarding the structural-spatial organization, technical infrastructure, and organizational matters, among others. The typology was further examined in the context of previous groupings in published literature. This novel approach of analyzing and structuring temporary housing offers a comprehensive perspective that can work as a universal understanding and language for precise communication among different disciplines regarding temporary housing.

Synthetic biology approaches in regulation of targeted gene expression

2021 ◽  
Vol 63 ◽  
pp. 102036
Author(s):  
Debao Huang ◽  
Pawel Z. Kosentka ◽  
Wusheng Liu
Keyword(s):  
Gene Expression ◽  
Synthetic Biology ◽  
Targeted Gene Expression

scholarly journals Improving cell-free glycoprotein synthesis by characterizing and enriching native membrane vesicles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jasmine M. Hershewe ◽  
Katherine F. Warfel ◽  
Shaelyn M. Iyer ◽  
Justin A. Peruzzi ◽  
Claretta J. Sullivan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Synthetic Biology ◽  
Membrane Protein ◽  
Membrane Vesicles ◽  
Processing Methods ◽  
Glycoprotein Synthesis ◽  
On Demand ◽  
Free Gene ◽  
Membrane Bound

AbstractCell-free gene expression (CFE) systems from crude cellular extracts have attracted much attention for biomanufacturing and synthetic biology. However, activating membrane-dependent functionality of cell-derived vesicles in bacterial CFE systems has been limited. Here, we address this limitation by characterizing native membrane vesicles in Escherichia coli-based CFE extracts and describing methods to enrich vesicles with heterologous, membrane-bound machinery. As a model, we focus on bacterial glycoengineering. We first use multiple, orthogonal techniques to characterize vesicles and show how extract processing methods can be used to increase concentrations of membrane vesicles in CFE systems. Then, we show that extracts enriched in vesicle number also display enhanced concentrations of heterologous membrane protein cargo. Finally, we apply our methods to enrich membrane-bound oligosaccharyltransferases and lipid-linked oligosaccharides for improving cell-free N-linked and O-linked glycoprotein synthesis. We anticipate that these methods will facilitate on-demand glycoprotein production and enable new CFE systems with membrane-associated activities.

scholarly journals Integrating metabolomics and targeted gene expression to uncover potential biomarkers of fungal/oomycetes-associated disease susceptibility in grapevine

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marisa Maia ◽  
António E. N. Ferreira ◽  
Rui Nascimento ◽  
Filipa Monteiro ◽  
Francisco Traquete ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plant Defence ◽  
Breeding Programs ◽  
Analysis Group ◽  
Expression Of Genes ◽  
Leucoanthocyanidin Reductase ◽  
Defence Responses ◽  
Targeted Gene Expression ◽  
Plant Defence Responses ◽  
First Time

Abstract Vitis vinifera, one of the most cultivated fruit crops, is susceptible to several diseases particularly caused by fungus and oomycete pathogens. In contrast, other Vitis species (American, Asian) display different degrees of tolerance/resistance to these pathogens, being widely used in breeding programs to introgress resistance traits in elite V. vinifera cultivars. Secondary metabolites are important players in plant defence responses. Therefore, the characterization of the metabolic profiles associated with disease resistance and susceptibility traits in grapevine is a promising approach to identify trait-related biomarkers. In this work, the leaf metabolic composition of eleven Vitis genotypes was analysed using an untargeted metabolomics approach. A total of 190 putative metabolites were found to discriminate resistant/partial resistant from susceptible genotypes. The biological relevance of discriminative compounds was assessed by pathway analysis. Several compounds were selected as promising biomarkers and the expression of genes coding for enzymes associated with their metabolic pathways was analysed. Reference genes for these grapevine genotypes were established for normalisation of candidate gene expression. The leucoanthocyanidin reductase 2 gene (LAR2) presented a significant increase of expression in susceptible genotypes, in accordance with catechin accumulation in this analysis group. Up to our knowledge this is the first time that metabolic constitutive biomarkers are proposed, opening new insights into plant selection on breeding programs.

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