Optimal resource allocation in micro-organisms under periodic nutrient fluctuations.

Although microorganisms often live in dynamic environments, most studies, both experimental and theoretical, are carried out under static conditions. In this work, we investigate the issue of optimal resource allocation in bacteria growing in periodic environments. We consider a dynamic model describing the microbial metabolism under varying conditions, involving a control variable quantifying the protein precursors allocation.

Optimal protein production by a synthetic microbial consortium: coexistence, distribution of labor, and syntrophy.

The bacterium E. coli is widely used to produce recombinant proteins such as growth hormone and insulin. One inconvenience with E.

Resource allocation accounts for the large variability of rate-yield phenotypes across bacterial strains.

Different strains of a microorganism growing in the same environment display a wide variety of growth rates and growth yields. We developed a coarse-grained model to test the hypothesis that different resource allocation strategies, corresponding to different compositions of the proteome, can account for the observed rate-yield variability. The model predictions were verified by means of a database of hundreds of published rate-yield and uptake-secretion phenotypes of strains grown in standard laboratory conditions.

Optimal proteome allocation and the temperature dependence of microbial growth laws.

Although the effect of temperature on microbial growth has been widely studied, the role of proteome allocation in bringing about temperature-induced changes remains elusive. To tackle this problem, we propose a coarse-grained model of microbial growth, including the processes of temperature-sensitive protein unfolding and chaperone-assisted (re)folding. We determine the proteome sector allocation that maximizes balanced growth rate as a function of nutrient limitation and temperature.

Global dynamics of the chemostat with overflow metabolism.

Fast growing E. coli cells, in glucose-aerobic conditions, excrete fermentation by-products such as acetate. This phenomenon is known as overflow metabolism and has been observed in a diverse range of microorganisms.

Optimal bacterial resource allocation: metabolite production in continuous bioreactors.

We show novel results addressing the problem of synthesizing a metabolite of interest in continuous bioreactors through resource allocation control. Our approach is based on a coarse-grained self-replicator dynamical model that accounts for microbial culture growth inside the bioreactor, and incorporates a synthetic growth switch that allows to externally modify the RNA polymerase concentration of the bacterial population, thus disrupting the natural process of allocation of available resources in bacteria. Further on, we study its asymptotic behavior using dynamical systems theory, and we provide conditions for the persistence of the bacterial population.

Insufficient quality of public automated external defibrillator recordings in the greater Paris area, a descriptive study.

Background: Western countries report a significant increase in the proportion of patients who experience out-of-hospital cardiac arrests (OHCAs) and benefit from a public automated external defibrillator (pAED) before the arrival of rescue teams. However, recordings of devices recovered after resuscitation are of variable quality. Analysis of these data may inform decisions of whether to implement an internal defibrillator for survivors, and provide useful information about the performance of pAED algorithms and the actions of bystanders.

Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs.

Synthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the conditions that make this possible, and of the trade-offs due to the concurrent growth of multiple species, is still limited. In this work, we contribute to filling this gap by the investigation of a known prototypical synthetic consortium.

Reducing a model of sugar metabolism in peach to catch different patterns among genotypes.

Several studies have been conducted to understand the dynamic of primary metabolisms in fruit by translating them into mathematics models. An ODE kinetic model of sugar metabolism has been developed by Desnoues et al. (2018) to simulate the accumulation of different sugars during peach fruit development.

Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial.

Research Question: Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)?

Design: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC.

Results: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.

Modeling the bioconversion of polysaccharides in a continuous reactor: A case study of the production of oligogalacturonates by .

In the quest for a sustainable economy of the Earth's resources and for renewable sources of energy, a promising avenue is to exploit the vast quantity of polysaccharide molecules contained in green wastes. To that end, the decomposition of pectin appears to be an interesting target because this polymeric carbohydrate is abundant in many fruit pulps and soft vegetables. To quantitatively study this degradation process, here we designed a bioreactor that is continuously fed with de-esterified pectin (PGA).

Analysis of a genetic-metabolic oscillator with piecewise linear models.

Interactions between gene regulatory networks and metabolism produce a diversity of dynamics, including multistability and oscillations. Here, we characterize a regulatory mechanism that drives the emergence of periodic oscillations in metabolic networks subject to genetic feedback regulation by pathway intermediates. We employ a qualitative formalism based on piecewise linear models to systematically analyze the behavior of gene-regulated metabolic pathways.

Optimal control of bacterial growth for the maximization of metabolite production.

Microorganisms have evolved complex strategies for controlling the distribution of available resources over cellular functions. Biotechnology aims at interfering with these strategies, so as to optimize the production of metabolites and other compounds of interest, by (re)engineering the underlying regulatory networks of the cell. The resulting reallocation of resources can be described by simple so-called self-replicator models and the maximization of the synthesis of a product of interest formulated as a dynamic optimal control problem.

Use of GBT013, a Collagen-Based Dressing, for the Healing of Diabetic Foot Ulcers.

The number of people with diabetes is expected to reach 592 million in the year 2035. Diabetic foot lesions are responsible for more hospitalizations than any other complication of diabetes. The aims of this study were to examine for the first time a new biocompatible and biodegradable tridimensional collagen-based matrix, GBT013, in humans for diabetic foot ulcer wound healing and to evaluate its ease of use to better define a protocol for a future clinical trial.

Principal process analysis of biological models.

Background: Understanding the dynamical behaviour of biological systems is challenged by their large number of components and interactions. While efforts have been made in this direction to reduce model complexity, they often prove insufficient to grasp which and when model processes play a crucial role. Answering these questions is fundamental to unravel the functioning of living organisms.

Reduction and Stability Analysis of a Transcription-Translation Model of RNA Polymerase.

The aim of this paper is to analyze the dynamical behavior of biological models of gene transcription and translation. We focus on a particular positive feedback loop governing the synthesis of RNA polymerase, needed for transcribing its own gene. We write a high-dimension model based on mass action laws and reduce it to a two-variable model (RNA polymerase and its mRNA) by means of monotone system theory and timescale arguments.

Mathematical modelling of microbes: metabolism, gene expression and growth.

The growth of microorganisms involves the conversion of nutrients in the environment into biomass, mostly proteins and other macromolecules. This conversion is accomplished by networks of biochemical reactions cutting across cellular functions, such as metabolism, gene expression, transport and signalling. Mathematical modelling is a powerful tool for gaining an understanding of the functioning of this large and complex system and the role played by individual constituents and mechanisms.

Efficacy of a collagen-based dressing in an animal model of delayed wound healing.

Objective: The aim of this study was to evaluate in vitro and in vivo the efficacy of GBT013, a collagen-based dressing, for the treatment of chronic wounds, in a db/db mouse model of diabetes.

Method: Macroscopic and histologic analyses of db/db mice wound healing with GBT013 or saline gauze were assessed. The mRNA expression and the proliferation of dermal fibroblast were investigated.

Dynamical Allocation of Cellular Resources as an Optimal Control Problem: Novel Insights into Microbial Growth Strategies.

Microbial physiology exhibits growth laws that relate the macromolecular composition of the cell to the growth rate. Recent work has shown that these empirical regularities can be derived from coarse-grained models of resource allocation. While these studies focus on steady-state growth, such conditions are rarely found in natural habitats, where microorganisms are continually challenged by environmental fluctuations.

Increased pregnancy rate using standardized coculture on autologous endometrial cells and single blastocyst transfer : a multicentre randomized controlled trial.

Despite excellent published results, the lack of well-designed, multicentre, randomized clinical trials results in an absence of general consensus on the efficacy of autologous endometrial cells coculture (AECC) in Assisted Reproductive Technology (ART). An open, multicentre, prospective, randomized controlled trial was designed to compare the pregnancy rate (PR) after the transfer of one blastocyst on day 5 after AECC to the transfer of one embryo on day 3 (control group). Patients were women aged 18 to 36, undergoing an ART cycle with no more than 1 embryo transfer failure.

Links between topology of the transition graph and limit cycles in a two-dimensional piecewise affine biological model.

A class of piecewise affine differential (PWA) models, initially proposed by Glass and Kauffman (in J Theor Biol 39:103-129, 1973), has been widely used for the modelling and the analysis of biological switch-like systems, such as genetic or neural networks. Its mathematical tractability facilitates the qualitative analysis of dynamical behaviors, in particular periodic phenomena which are of prime importance in biology. Notably, a discrete qualitative description of the dynamics, called the transition graph, can be directly associated to this class of PWA systems.

Global stability of enzymatic chains of full reversible Michaelis-Menten reactions.

We consider a chain of metabolic reactions catalyzed by enzymes, of reversible Michaelis-Menten type with full dynamics, i.e. not reduced with any quasi-steady state approximations.

Global stability of reversible enzymatic metabolic chains.

We consider metabolic networks with reversible enzymatic reactions. The model is written as a system of ordinary differential equations, possibly with inputs and outputs. We prove the global stability of the equilibrium (if it exists), using techniques of monotone systems and compartmental matrices.

Stabilizing effect of cannibalism in a two stages population model.

In this paper we build a prey-predator model with discrete weight structure for the predator. This model will conserve the number of individuals and the biomass and both growth and reproduction of the predator will depend on the food ingested. Moreover the model allows cannibalism which means that the predator can eat the prey but also other predators.