Antagonistic control of a dual-input mammalian gene switch by food additives

Synthetic biology has significantly advanced the design of mammalian trigger-inducible transgene-control devices that are able to programme complex cellular behaviour. Fruit-based benzoate derivatives licensed as food additives, such as flavours (e.g. vanillate) and preservatives (e.g. benzoate), are a particularly attractive class of trigger compounds for orthogonal mammalian transgene control devices because of their innocuousness, physiological compatibility and simple oral administration. Capitalizing on the genetic componentry of the soil bacterium Comamonas testosteroni, which has evolved to catabolize a variety of aromatic compounds, we have designed different mammalian gene expression systems that could be induced and repressed by the food additives benzoate and vanillate. When implanting designer cells engineered for gene switch-driven expression of the human placental secreted alkaline phosphatase (SEAP) into mice, blood SEAP levels of treated animals directly correlated with a benzoate-enriched drinking programme. Additionally, the benzoate-/vanillate-responsive device was compatible with other transgene control systems and could be assembled into higher-order control networks providing expression dynamics reminiscent of a lap-timing stopwatch. Designer gene switches using licensed food additives as trigger compounds to achieve antagonistic dual-input expression profiles and provide novel control topologies and regulation dynamics may advance future gene- and cell-based therapie

A personal route prediction system based on trajectory data mining

This paper presents a system where the personal route of a user is predicted using a probabilistic model built from the historical trajectory data. Route patterns are extracted from personal trajectory data using a novel mining algorithm, Continuous Route Pattern Mining (CRPM), which can tolerate different kinds of disturbance in trajectory data. Furthermore, a client–server architecture is employed which has the dual purpose of guaranteeing the privacy of personal data and greatly reducing the computational load on mobile devices. An evaluation using a corpus of trajectory data from 17 people demonstrates that CRPM can extract longer route patterns than current methods. Moreover, the average correct rate of one step prediction of our system is greater than 71%, and the average Levenshtein distance of continuous route prediction of our system is about 30% shorter than that of the Markov model based method

Biosynthesis, characterization, and antifungal activity of plant-mediated silver nanoparticles using Cnidium monnieri fruit extract

The present study describes a novel method for green synthesis of silver nanoparticles using Cnidium monnieri (CM-AgNPs). Cnidium monnieri fruit is an excellent anti tinea drug that can be used externally to treat superficial fungal infections in the human body. The aqueous ethanolic extract of Cnidium monnieri fruit was prepared and employed in the synthesis of stable silver nanoparticles via biological reduction method. The synthesis conditions of CM-AgNPs was systematically optimized using Box–Behnken design. CM-AgNPs were well characterized by UV-spectroscopy and X-ray powder diffraction (XRD), and it was confirmed that the synthesized particles were AgNPs. The possible functional groups required for the reduction and stabilization of CM-AgNPs in the extract were identified through FTIR spectrum. The size of CM-AgNPs structure was confirmed to be approximately 44.6 nm in polydisperse spherical shape through scanning electron microscopy (SEM), transmission electron microscopy (TEM), and laser dynamic light scattering (DLS). Further, the minimum inhibitory concentration 90% (MIC90) ratios values of Cm-AgNPs against Trichophyton rubrum (7 d), T. mentagrophytes (7 d) and Candida albicans (24 h) were 3.125, 3.125, and 0.78125 μg/mL, respectively, determined by the broth micro dilution method. Finally, the result was concluded that the synthesized AgNPs could be further evaluated in large scale as a potential human topical antifungal agent

A synthetic biology-based device prevents liver injury in mice

BACKGROUND & AIMS The liver performs a panoply of complex activities coordinating metabolic, immunologic and detoxification processes. Despite the liver's robustness and unique self-regeneration capacity, viral infection, autoimmune disorders, fatty liver disease, alcohol abuse and drug-induced hepatotoxicity contribute to the increasing prevalence of liver failure. Liver injuries impair the clearance of bile acids from the hepatic portal vein which leads to their spill over into the peripheral circulation where they activate the G-protein-coupled bile acid receptor TGR5 to initiate a variety of hepatoprotective processes. METHODS By functionally linking activation of ectopically expressed TGR5 to an artificial promoter controlling transcription of the hepatocyte growth factor (HGF), we created a closed-loop synthetic signalling network that coordinated liver injury-associated serum bile acid levels to expression of HGF in a self-sufficient, reversible and dose-dependent manner. RESULTS After implantation of genetically engineered human cells inside auto-vascularizing, immunoprotective and clinically validated alginate-poly-(L-lysine)-alginate beads into mice, the liver-protection device detected pathologic serum bile acid levels and produced therapeutic HGF levels that protected the animals from acute drug-induced liver failure. CONCLUSIONS Genetically engineered cells containing theranostic gene circuits that dynamically interface with host metabolism may provide novel opportunities for preventive, acute and chronic healthcare. LAY SUMMARY Liver diseases leading to organ failure may go unnoticed as they do not trigger any symptoms or significant discomfort. We have designed a synthetic gene circuit that senses excessive bile acid levels associated with liver injuries and automatically produces a therapeutic protein in response. When integrated into mammalian cells and implanted into mice, the circuit detects the onset of liver injuries and coordinates the production of a protein pharmaceutical which prevents liver damage