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PubMed | University of Basel, ETH Zurich and Institute University Of Technology
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2016

Graves disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus-pituitary-thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor- fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus-pituitary-thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies.


Mahamat A.D.,University of South Africa | Hamid O.I.,University of South Africa | Soultan M.,University of South Africa | Khayal M.Y.,Mohammed V University | And 3 more authors.
Research Journal of Applied Sciences, Engineering and Technology | Year: 2015

The excessive consumption of energy in the building sector weighs heavily on the energy bill of the developing countries. It is for this reason that several studies have been carried out at the international level, both at the level of building's envelope and equipments, in order to contribute to the control of energy. In this study, we are interested in studying the effect of cow's dung on the thermo-physical characteristics of materials based on clay in the region of Abeche (Chad). The goal is to obtain light weighs samples with better thermal performance, which can contribute to improve the thermal comfort in traditional constructions in Chad and to reduce the use of cereal's straw and pods. Since these are used to feed livestock. The experimental study that we have conducted has enabled us to determine the conductivity, the effusivity and the thermal diffusivity of our samples. Our experimental data show a good efficiency and a significant decrease in the thermal conductivity of material with cow's dung compared to simple clay material. © Maxwell Scientific Organization, 2015.


Fais T.,French Institute of Health and Medical Research | Fais T.,Center Hospitalier University | Delmas J.,French Institute of Health and Medical Research | Delmas J.,Center Hospitalier University | And 6 more authors.
Gut Microbes | Year: 2016

Most cases of colorectal cancer (CRC) are sporadic, and numerous studies have suggested that gut microbiota may play a crucial role in CRC development. Escherichia coli is a member of the gut microbiota frequently associated with colorectal tumors. CRC-associated E. coli strains frequently harbor the pks genomic island. This genomic island is responsible for the synthesis of colibactin genotoxin, which increases tumor numbers in CRC mouse models. We recently showed that targeting ClbP, a key enzyme involved in colibactin synthesis, blocks the deleterious effect of this toxin in vitro and leads to a significant decrease in tumor numbers in vivo. Altogether, our results suggest that the personalized treatment of CRC should also take into consideration the bacteria associated with the tumor in order to limit their deleterious effects. © 2016 Taylor & Francis Group, LLC

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