Search results for "Mod"

In cutaneous leishmaniasis, induction of retinoic acid in skin-derived Langerhans cells is not sufficient for induction of parasite persistence-media…

2017

Post-transcriptional bursting in genes regulated by small RNA molecules

2018

Gene expression programs in living cells are highly dynamic due to spatiotemporal molecular signaling and inherent biochemical stochasticity. Here we study a mechanism based on molecule-to-molecule variability at the RNA level for the generation of bursts of protein production, which can lead to heterogeneity in a cell population. We develop a mathematical framework to show numerically and analytically that genes regulated post transcriptionally by small RNA molecules can exhibit such bursts due to different states of translation activity (on or off), mostly revealed in a regime of few molecules. We exploit this framework to compare transcriptional and post-transcriptional bursting and also…

Towards more sustainable food systems. Addressing food waste at school canteens

2018

Food Waste is a global significant issue for ethical, environmental and economic reasons, while its management is difficult due to its frequent low visibility. Individual choices and preferences are closely related to the generation of food waste although likely to be modified through education and awareness campaigns. In particular, school canteens are big generators of food waste and, at the same time, provide a great opportunity to improve habits regarding nutrition and education on sustainability, thus impacting the future of the food system. The end purpose of this research is identifying the causes of food waste and unveiling best practices towards its reduction. To achieve this goal,…

Progressive Characterization of Visual Phenotype in Bardet-Biedl Syndrome Mutant Mice

2019

Purpose Bardet-Biedl syndrome (BBS) is an archetypical ciliopathy caused by defective ciliary trafficking and consequent function. Insights gained from BBS mouse models are applicable to other syndromic and nonsyndromic retinal diseases. This progressive characterization of the visual phenotype in three BBS mouse models sets a baseline for testing therapeutic interventions. Methods Longitudinal acquisition of electroretinograms, optical coherence tomography scans, and visual acuity using the optomotor reflex in Bbs6/Mkks, Bbs8/Ttc8, and Bbs5 knockout mice. Gene and protein expression analysis in vivo and in vitro. Results Complete loss of BBS5, BBS6, or BBS8 leads to different rates of reti…

Usherin defects lead to early-onset retinal dysfunction in zebrafish

2018

Mutations in USH2A are the most frequent cause of Usher syndrome and autosomal recessive nonsyndromic retinitis pigmentosa. To unravel the pathogenic mechanisms underlying USH2A-associated retinal degeneration and to evaluate future therapeutic strategies that could potentially halt the progression of this devastating disorder, an animal model is needed. The available Ush2a knock-out mouse model does not mimic the human phenotype, because it presents with only a mild and late-onset retinal degeneration. Using CRISPR/Cas9-technology, we introduced protein-truncating germline lesions into the zebrafish ush2a gene (ush2a(rmc1): c.2337_2342delinsAC; p.Cys780GlnfsTer32 and ush2a(b1245): c.15520_…

Generation of an inducible RPE-specific Cre transgenic-mouse line.

2018

The retinal pigment epithelium (RPE) is an epithelial monolayer in the back of the vertebrate eye. RPE dysfunction is associated with retinal degeneration and blindness. In order to fully understand how dysregulation affects visual function, RPE-specific gene knockouts are indispensable. Since the currently available RPE-specific Cre recombinases show lack of specificity or poor recombination, we sought to generate an alternative. We generated a tamoxifen-inducible RPE-specific Cre transgenic mouse line under transcriptional control of an RPE-specific Tyrosinase enhancer. We characterized the Cre-mediated recombinant expression by crossing our RPE-Tyrosinase-CreErT2 mouse line with the tdTo…

Quantitative characterization of translational riboregulators using an in vitro transcription–translation system

2018

Riboregulators are short RNA sequences that, upon binding to a ligand, change their secondary structure and influence the expression rate of a downstream gene. They constitute an attractive alternative to transcription factors for building synthetic gene regulatory networks because they can be engineered de novo. However, riboregulators are generally designed in silico and tested in vivo, which provides little quantitative information about their performances, thus hindering the improvement of design algorithms. Here we show that a cell-free transcription-translation (TX-TL) system provides valuable information about the performances of in silico designed riboregulators. We first propose a …

Temperature changes in 2% chlorhexidine gluconate using two activation methods with different intensity levels

2018

Background Chlorhexidine is an irrigant solution widely used in root canal treatment because of its good antimicrobial properties. However, its mixture with sodium hypochlorite results in the appearance of substance called p-chloroaniline, a cytotoxic substance. This is also found when chlorhexidine is heated. The use of passive ultrasonic irrigation is related to an irrigant thermal increase, which can cause the appearance of p-chloroaniline. Thus, the objective is to establish the influence of ultrasonic and sonic activation, with the use of different intensities, upon the temperature of chlorhexidine gluconate (CHX). Material and methods The following groups were established: control (wi…

Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib

2017

IL-6 is a central mediator of the immediate induction of hepatic acute phase proteins (APP) in the liver during infection and after injury, but increased IL-6 activity has been associated with multiple pathological conditions. In hepatocytes, IL-6 activates JAK1-STAT3 signaling that induces the negative feedback regulator SOCS3 and expression of APPs. While different inhibitors of IL-6-induced JAK1-STAT3-signaling have been developed, understanding their precise impact on signaling dynamics requires a systems biology approach. Here we present a mathematical model of IL-6-induced JAK1-STAT3 signaling that quantitatively links physiological IL-6 concentrations to the dynamics of IL-6-induced …

Nuclear inclusions of pathogenic ataxin-1 induce oxidative stress and perturb the protein synthesis machinery

2020

Spinocerebellar ataxia type-1 (SCA1) is caused by an abnormally expanded polyglutamine (polyQ) tract in ataxin-1. These expansions are responsible for protein misfolding and self-assembly into intranuclear inclusion bodies (IIBs) that are somehow linked to neuronal death. However, owing to lack of a suitable cellular model, the downstream consequences of IIB formation are yet to be resolved. Here, we describe a nuclear protein aggregation model of pathogenic human ataxin-1 and characterize IIB effects. Using an inducible Sleeping Beauty transposon system, we overexpressed the ATXN1(Q82) gene in human mesenchymal stem cells that are resistant to the early cytotoxic effects caused by the expr…