Biology subjects

Leclere, M.

Publications and source records attributed to Leclere, M..

3 recordsLinked to original sources

bioRxiv2020

Severe asthma is associated with a remodeling of the pulmonary arteries in horses.

Pulmonary hypertension and cor pulmonale are complications of severe equine asthma, as a consequence of pulmonary hypoxic vasoconstriction. However, as pulmonary hypertension is only partially reversible by oxygen administration, other etiological factors are likely involved. In human chronic obstructive pulmonary disease, pulmonary artery remodeling contributes to the development of pulmonary hypertension. In rodent models, pulmonary vascular remodeling is present as a consequence of allergic airway inflammation. The present study investigated the presence of remodeling of the pulmonary arteries in severe equine asthma, its distribution throughout the lungs, and its reversibility following long-term antigen avoidance strategies and inhaled corticosteroid administration. Using histomorphometry, the total wall area of pulmonary arteries from different regions of the lung of asthmatic horses and controls was measured. The smooth muscle mass of pulmonary arteries was also estimated on lung sections stained for -smooth muscle actin. Reversibility of vascular changes in asthmatic horses was assessed after 1 year of antigen avoidance alone or treatment with inhaled fluticasone. Pulmonary arteries showed increased wall area in apical and caudodorsal lung regions of asthmatic horses in both exacerbation and remission. The pulmonary arteries smooth muscle mass was similarly increased. Both treatments reversed the increase in wall area. However, normalization of the vascular smooth muscle mass was observed only after treatment with antigen avoidance, but not with fluticasone. In conclusion, severe equine asthma is associated with remodeling of the pulmonary arteries consisting in an increased smooth muscle mass. The resulting narrowing of the artery lumen could enhance hypoxic vasoconstriction, contributing to pulmonary hypertension. Vascular smooth muscle mass normalization is better achieved by antigen avoidance than with inhaled corticosteroids.

pathology↗

bioRxiv2019

Exploring the design space of recombinase logic circuits.

Logic circuits operating in living cells are generally built by mimicking electronic layouts, and scale-up is accomplished using additional layers of elementary logic gates like NOT and NOR gates. Recombinase-based logic, in which logic is implemented using DNA inversion or excision, allows for highly efficient, compact and single-layer design architectures. However, recombinase logic architectures depart from electronic design principles, and gate design performed empirically is challenging for an increasing number of inputs. Here we used a combinatorial approach to explore the design space of recombinase logic devices. We generated combinations and permutations of recombination sites, genes, and regulatory elements, for a total of ~19 million designs supporting the implementation of all 2- and 3-input logic functions and up to 92% of 4-input logic functions. We estimated the influence of different design constraints on the number of executable functions, and found that the use of DNA inversion and transcriptional terminators were key factors to implement the vast majority of logic functions. We provide a user-friendly interface, called RECOMBINATOR (http://recombinator.lirmm.fr/index.php), that enable users to navigate the design space of recombinase-based logic, find architectures implementing a specific logic function and sort them according to various biological criteria. Finally, we define a set of 16 architectures from which all 256 3-input logic functions can be derived. This work provides a theoretical foundation for the systematic exploration and design of single-layer recombinase logic devices.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=55 SRC=\"FIGDIR/small/711374v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (14K):\norg.highwire.dtl.DTLVardef@799feborg.highwire.dtl.DTLVardef@f22dc2org.highwire.dtl.DTLVardef@19a1d10org.highwire.dtl.DTLVardef@ea3b9a_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2017

Scalable composition frameworks for multicellular logic

A major goal of synthetic biology is to reprogram living organisms to solve pressing challenges in manufacturing, environmental remediation, or healthcare. While many types of genetic logic gates have been engineered, their scalability remains limited. Previous work demonstrated that Distributed Multicellular Computation (DMC) enables the implementation of complex logic within cellular consortia. However, current DMC systems require spatial separation of cellular subpopulation to be scalable to N-inputs, and need cell-cell communication channels to operate. Here we present scalable composition frameworks for the systematic design of multicellular consortia performing recombinase-based Boolean or history-dependent logic, and integrating an arbitrary number of inputs. The theoretical designs for both Boolean and history-dependent logic are based on reduced sets of computational modules implemented into specific cellular subpopulations which can then be combined in various manners to implement all logic functions. Our systems mark a departure from previous DMC architectures as they do not require either cell-cell communication nor spatial separation, greatly facilitating their implementation and making them fully autonomous. Due to their scalability and composability, we anticipate that the design strategies presented here will help researchers and engineers to reprogram cellular behavior for various applications in a streamlined manner. We provide an online tool for automated design of DNA architectures allowing the implementation of multicellular N-inputs logic functions at: http://synbio.cbs.cnrs.fr/calin.

synthetic biology↗