scholarly journals Multiplexed Cell-Based Diagnostic Devices for Detection of Renal Biomarkers Using Genetic Circuits

2021 ◽  
Author(s):  
Sila Kose ◽  
Recep Ahan ◽  
Ilkay Koksaldi ◽  
Muazzez Olgac ◽  
Cigdem Kasapkara ◽  
...  
Keyword(s):  
Control Strategies ◽  
Low Cost ◽  
Logic Gate ◽  
Genetic Circuits ◽  
Major Health ◽  
Expression Control ◽  
Renal Biomarkers ◽  
Gene Expression Control ◽  
Response Profiles ◽  
Operational Range

The number of synthetic biology based solutions employed in the medical industry is growing every year. The whole cell biosensors being one of them, have been proven valuable tools for developing low-cost, portable, personalized medicine alternatives to conventional techniques. Based on this concept, we targeted one of the major health problems in the world, Chronic Kidney Disease (CKD). To do so, we developed two novel biosensors for the detection of two important renal biomarkers; urea and uric acid. Using advanced gene expression control strategies we improved the operational range and the response profiles of each biosensor to meet clinical specifications. We further engineered these systems to enable multiplexed detection as well as an AND-logic gate operating system. Finally, we tested the applicability of these systems and optimized their working dynamics inside complex medium human blood serum. This study could help the efforts to transition from labor-intensive and expensive laboratory techniques to widely available, portable, low cost diagnostic options.

scholarly journals High-performance chemical- and light-inducible recombinases in mammalian cells and mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Benjamin H. Weinberg ◽  
Jang Hwan Cho ◽  
Yash Agarwal ◽  
N. T. Hang Pham ◽  
Leidy D. Caraballo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
High Performance ◽  
Genome Engineering ◽  
Genetic Circuits ◽  
Control Of Gene Expression ◽  
Expression Control ◽  
Gene Expression Control ◽  
High Performance Systems ◽  
Spatiotemporal Control

Abstract Site-specific DNA recombinases are important genome engineering tools. Chemical- and light-inducible recombinases, in particular, enable spatiotemporal control of gene expression. However, inducible recombinases are scarce due to the challenge of engineering high performance systems, thus constraining the sophistication of genetic circuits and animal models that can be created. Here we present a library of >20 orthogonal inducible split recombinases that can be activated by small molecules, light and temperature in mammalian cells and mice. Furthermore, we engineer inducible split Cre systems with better performance than existing systems. Using our orthogonal inducible recombinases, we create a genetic switchboard that can independently regulate the expression of 3 different cytokines in the same cell, a tripartite inducible Flp, and a 4-input AND gate. We quantitatively characterize the inducible recombinases for benchmarking their performances, including computation of distinguishability of outputs. This library expands capabilities for multiplexed mammalian gene expression control.

scholarly journals UNIGEMS: plasmids and parts to facilitate teaching on assembly, gene expression control and logic in E. coli

2021 ◽  
Author(s):  
Alex Siddall ◽  
Abbie Ann Williams ◽  
Jason Sanders ◽  
Jai A Denton ◽  
Dean Madden ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synthetic Biology ◽  
Logic Gate ◽  
Undergraduate Teaching ◽  
Gibson Assembly ◽  
E Coli ◽  
Expression Control ◽  
Gene Expression Control ◽  
Plasmid Backbone ◽  
High Copy Plasmid

Synthetic biology is as an excellent vehicle for education, as it enables creativecombination of engineering and molecular biology approaches for quantitative charac-terisations of the assembled constructs. However, there is a limited number of resourcesavailable for such applications in the educational context, where straightforward setup, easily measurable phenotypes and extensibility are of particular importance. To expandthe availability of education-friendly resources to teach synthetic biology and geneticengineering, we developed Unigems, a set of 10 plasmids that enable out-of-the-boxinvestigations of principles of gene expression control, as well as more complex designs- a biological logic gate. The system uses a common high-copy plasmid backbone anda common set of primers to enable Gibson-assembly of PCR-generated or synthesisedparts into a target vector. It currently has two reporter genes with either two consti-tutive (high- or low-level) or two inducible (lactose- or arabinose-) promoters, as wellas a single-plasmid implementation of an AND logic gate. The Unigems system hasalready been employed in undergraduate teaching settings, during outreach events andfor training of iGEM teams. All plasmids have been deposited in Addgene.

scholarly journals An Agent-Based Crop Model Framework for Heterogeneous Soils

Agronomy ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 85
Author(s):  
Jorge Lopez-Jimenez ◽  
Nicanor Quijano ◽  
Alain Vande Wouwer
Keyword(s):  
Growth Models ◽  
Control Strategies ◽  
Low Cost ◽  
Soil Heterogeneity ◽  
Crop Growth ◽  
Negative Effects ◽  
Model Framework ◽  
Agent Based ◽  
Crop Growth Models ◽  
Definition Of

Climate change and the efficient use of freshwater for irrigation pose a challenge for sustainable agriculture. Traditionally, the prediction of agricultural production is carried out through crop-growth models and historical records of the climatic variables. However, one of the main flaws of these models is that they do not consider the variability of the soil throughout the cultivation area. In addition, with the availability of new information sources (i.e., aerial or satellite images) and low-cost meteorological stations, it is convenient that the models incorporate prediction capabilities to enhance the representation of production scenarios. In this work, an agent-based model (ABM) that considers the soil heterogeneity and water exchanges is proposed. Soil heterogeneity is associated to the combination of individual behaviours of uniform portions of land (agents), while water fluxes are related to the topography. Each agent is characterized by an individual dynamic model, which describes the local crop growth. Moreover, this model considers positive and negative effects of water level, i.e., drought and waterlogging, on the biomass production. The development of the global ABM is oriented to the future use of control strategies and optimal irrigation policies. The model is built bottom-up starting with the definition of agents, and the Python environment Mesa is chosen for the implementation. The validation is carried out using three topographic scenarios in Colombia. Results of potential production cases are discussed, and some practical recommendations on the implementation are presented.

scholarly journals Transcriptomic uniqueness and commonality of the ion channels and transporters in the four heart chambers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sanda Iacobas ◽  
Bogdan Amuzescu ◽  
Dumitru A. Iacobas
Keyword(s):  
Ion Channels ◽  
Cycle Phase ◽  
Functional Roles ◽  
Expression Control ◽  
Gene Expression Control ◽  
Left And Right ◽  
The Right ◽  
Phase Out ◽  
Right Atria ◽  
Agilent Microarrays

AbstractMyocardium transcriptomes of left and right atria and ventricles from four adult male C57Bl/6j mice were profiled with Agilent microarrays to identify the differences responsible for the distinct functional roles of the four heart chambers. Female mice were not investigated owing to their transcriptome dependence on the estrous cycle phase. Out of the quantified 16,886 unigenes, 15.76% on the left side and 16.5% on the right side exhibited differential expression between the atrium and the ventricle, while 5.8% of genes were differently expressed between the two atria and only 1.2% between the two ventricles. The study revealed also chamber differences in gene expression control and coordination. We analyzed ion channels and transporters, and genes within the cardiac muscle contraction, oxidative phosphorylation, glycolysis/gluconeogenesis, calcium and adrenergic signaling pathways. Interestingly, while expression of Ank2 oscillates in phase with all 27 quantified binding partners in the left ventricle, the percentage of in-phase oscillating partners of Ank2 is 15% and 37% in the left and right atria and 74% in the right ventricle. The analysis indicated high interventricular synchrony of the ion channels expressions and the substantially lower synchrony between the two atria and between the atrium and the ventricle from the same side.

scholarly journals A Novel Longitudinal Speed Estimator for Four-Wheel Slip in Snowy Conditions

2021 ◽  
Vol 11 (6) ◽  
pp. 2809
Author(s):  
Dongmin Zhang ◽  
Qiang Song ◽  
Guanfeng Wang ◽  
Chonghao Liu
Keyword(s):  
Control Strategies ◽  
Low Cost ◽  
Estimation Error ◽  
Slip Rate ◽  
Vehicle Speed ◽  
Acceleration Sensor ◽  
Wheel Slip ◽  
Longitudinal Acceleration ◽  
Tire Rotation ◽  
Speed Estimator

This article proposes a novel longitudinal vehicle speed estimator for snowy roads in extreme conditions (four-wheel slip) based on low-cost wheel speed encoders and a longitudinal acceleration sensor. The tire rotation factor, η, is introduced to reduce the deviation between the rotation tire radius and the manufacturer’s marked tire radius. The Local Vehicle Speed Estimator is defined to eliminate longitudinal vehicle speed estimation error. It improves the tire slip accuracy of four-wheel slip, even with a high slip rate. The final vehicle speed is estimated using two fuzzy control strategies that use vehicle speed estimates from speed encoders and a longitudinal acceleration sensor. Experimental and simulation results confirm the algorithm’s validity for estimating longitudinal vehicle speed for four-wheel slip in snowy road conditions.

Low-cost BSA technique for threshold-logic gate based multiplier implementations

1997 ◽  
Vol 33 (12) ◽  
pp. 1028
Author(s):  
J.M. Quintana ◽  
M.J. Avedillo ◽  
A. Rueda
Keyword(s):  
Low Cost ◽  
Logic Gate ◽  
Threshold Logic

scholarly journals Repression of Prespliceosome Complex Formation at Two Distinct Steps by Fox-1/Fox-2 Proteins

2008 ◽  
Vol 28 (17) ◽  
pp. 5507-5516 ◽  
Author(s):  
Hua-Lin Zhou ◽  
Hua Lou
Keyword(s):  
Alternative Splicing ◽  
Complex Formation ◽  
Biochemical Analysis ◽  
Expression Control ◽  
Regulatory Strategy ◽  
Gene Expression Control ◽  
Splicing Regulator ◽  
Specific Alternative ◽  
Novel Strategy ◽  
Robust Regulation

ABSTRACT Precise and robust regulation of alternative splicing provides cells with an essential means of gene expression control. However, the mechanisms that ensure the tight control of tissue-specific alternative splicing are not well understood. It has been demonstrated that robust regulation often results from the contributions of multiple factors to one particular splicing pathway. We report here a novel strategy used by a single splicing regulator that blocks the formation of two distinct prespliceosome complexes to achieve efficient regulation. Fox-1/Fox-2 proteins, potent regulators of alternative splicing in the heart, skeletal muscle, and brain, repress calcitonin-specific splicing of the calcitonin/CGRP pre-mRNA. Using biochemical analysis, we found that Fox-1/Fox-2 proteins block prespliceosome complex formation at two distinct steps through binding to two functionally important UGCAUG elements. First, Fox-1/Fox-2 proteins bind to the intronic site to inhibit SF1-dependent E′ complex formation. Second, these proteins bind to the exonic site to block the transition of E′ complex that escaped the control of the intronic site to E complex. These studies provide evidence for the first example of regulated E′ complex formation. The two-step repression of presplicing complexes by a single regulator provides a powerful and accurate regulatory strategy.

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