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    Evolution of pH-sensitive transcription termination during adaptation to repeated long-term starvation

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    Abstract Fluctuating environments that consist of regular cycles of co-occurring stress are a common challenge faced by cellular populations. For a population to thrive in constantly changing conditions, an ability to coordinate a rapid cellular response is essential. Here, we identify a mutation conferring an arginine-to-histidine (Arg to His) substitution in the transcription terminator Rho. The rho R109H mutation frequently arose in E. coli populations experimentally evolved under repeated long-term starvation conditions, during which feast and famine result in drastic environmental pH fluctuations. Metagenomic sequencing revealed that populations containing the rho mutation also possess putative loss-of-function mutations in ydcI , which encodes a recently characterized transcription factor associated with pH homeostasis. Genetic reconstructions of these mutations show that the rho allele confers a plastic alkaline-induced reduction of Rho function that, when found in tandem with a Δ ydcI allele, leads to intracellular alkalinization and genetic assimilation of Rho mutant function. We further identify Arg to His substitutions at analogous sites in rho alleles from species originating from fluctuating alkaline environments. Our results suggest that Arg to His substitutions in global regulators of gene expression can serve to rapidly coordinate complex responses through pH sensing and shed light on how cellular populations across the tree of life use environmental cues to coordinate rapid responses to complex, fluctuating environments

    Some Comparison Results for First-Order Hamilton-Jacobi Equations and Second-Order Fully Nonlinear Parabolic Equations with Ventcell Boundary Conditions

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    International audienceIn this article, we consider fully nonlinear, possibly degenerate, parabolic equations associated with Ventcell boundary conditions in bounded or unbounded, smooth domains. We first analyze the exact form of such boundary conditions in general domains in order that the notion of viscosity solutions make sense. Then we prove general comparison results under natural assumptions on the nonlinearities, assuming only that the equation is either coercive (first-order case) or strictly elliptic (second-order case) in the normal direction in a neighborhood of the boundary. Our method is inspired by the ``twin blow-up method'' of Forcadel-Imbert-Monneau and ideas of Lions-Souganidis which we extend to the framework of Ventcell boundary conditions

    Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study

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    RéoLoc : Réorganisation dynamique des caractères sur un clavier à défilement automatique ligne/colonne

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    International audiencePeople with disabilities have difficulties in accessing usuals pointing devices and to input text. To answer this need, several aids have been developed, including virtual keyboards. For people with limited functional mobility, scanning access is given priority. Even if a large scanning mode exists, the text input speed (TIS) is still slow. In aims to increase this TIS, some keyboards are augmented with character prediction modules. Nonetheless, this prediction is in reality used only with linear scanning. This article presents RéoLoc an intraline approach to character prediction that can be integrated with line-column scanning. Two types of RéoLoc have been the subject of a user study and compared in term of text input speed to a static keyboard.Les personnes ayant des déficiences sensorimotrices rencontrent des difficultés à accéder aux dispositifs de pointage habituels et à la saisie de texte. Pour répondre à ces besoins, de multiples aides ont été développées prenant la forme de claviers virtuels. Pour les personnes ne disposant que de peu de mouvements fonctionnels, un accès par défilement sur ces claviers est privilégié. Cependant, la saisie sur ces dispositifs reste relativement lente et fatigante. Afin d'augmenter la vitesse de saisie, l'utilisation d'une prédiction de caractères permet une réorganisation contextuelle des caractères sur le clavier. Néanmoins, cette dernière n'est, en pratique, utilisée qu'avec un défilement linéaire. Cet article présente RéoLoc une approche intra ligne de la prédiction de caractères permettant son intégration avec un défilement ligne/colonne. Deux types de configurations RéoLoc ont fait l'objet d'une étude utilisateurs et ont montré leur intérêt, notamment en termes de vitesse de saisie comparé à un clavier statique

    Modeling compartmentalization within intracellular signaling pathway

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    We present a novel approach to modeling receptor-activated signaling pathways that take into account the compartmentalization of receptors and their effectors, both on the cell surface and in dynamic intracellular vesicles called endosomes. The first building block of the model concerns compartment dynamics. It takes into account creation of de novo endosomes, i.e. endocytosis, and further recycling of endosomes to the cell surface or degradation, as well as fusion of endosomes via coagulation dynamics. The second building block concerns biochemical reactions on the cell surface and within intra-cellular compartments. Both building blocks are coupled by the transfer of molecules that occurs at each event that modifies the compartments.The model is formulated as a integro-partial differential equation, with transport and coagulation operators, and source terms, coupled to an integro-differential equation. In this work, we prove sufficient conditions to obtain exponential ergodicity for the size distribution of intracellular compartments. We further design a finite volume scheme to simulate our model. Finally, we show two application cases that show qualitative agreement with recently published data, proving that our model can help capture the spatio-temporal complexity of receptor-activated signaling pathway.Nous présentons une nouvelle approche de modélisation des voies de signalisation activées par les récepteurs, qui prend en compte la compartimentation des récepteurs et de leurs effecteurs, à la fois à la surface cellulaire et dans des vésicules intracellulaires dynamiques appelées endosomes. Le premier élément constitutif du modèle concerne la dynamique des compartiments. Il prend en compte la création d'endosomes de novo, c'est-à-dire l'endocytose, puis le recyclage des endosomes à la surface cellulaire ou leur dégradation, ainsi que la fusion des endosomes via une dynamique de coagulation. Le deuxième élément constitutif concerne les réactions biochimiques à la surface des cellules et dans chaque compartiment intracellulair. Les deux parties du modèles sont couplées par le transfert de molécules qui se produit à chaque événement modifiant les compartiments.Le modèle est formulé comme une équation aux dérivées partielles avec terme intégrale, avec des opérateurs de transport, de coagulation et des termes sources, couplée à une équation intégro-différentielle. Dans ce travail, nous prouvons des conditions suffisantes pour obtenir une ergodicité exponentielle pour la distribution en taille des compartiments intracellulaires. Nous concevons en outre un schéma de volumes finis pour simuler notre modèle. Enfin, nous montrons deux cas d'application qui montrent un accord qualitatif avec des données publiées récemment, prouvant que notre modèle peut aider à capturer la complexité spatio-temporelle de l'activation des voies de signalisation

    Exponential mixing of all orders for Arnol'd cat map lattices

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    22 pages LaTeX, uses utphys.bst for bibliography styleWe show that the recently introduced classical Arnol'd cat map lattice field theories, which are chaotic, are exponentially mixing to all orders. Their mixing times are well-defined and are expressed in terms of the Lyapunov exponents, more precisely by the combination that defines the inverse of the Kolmogorov-Sinai entropy of these systems. We prove by an explicit recursive construction of correlation functions, that these exhibit ll-fold mixing for any l= 3,4,5... This computation is relevant for Rokhlin's conjecture, which states that 2-fold mixing induces l-fold mixing for any l>2. Our results show that 2-fold exponential mixing, while being necessary for any ll-fold mixing to hold it is nevertheless not sufficient for Arnol'd cat map lattice field theories. The correspondence principle implies that these mixing times, also, control the scrambling of the underlying quantum system for short times

    Sustainable control of caprine reproduction through sociosexual interactions

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    International audienceReproductive seasonality is a characteristic of male and female goat breeds from temperate and subtropical latitudes. The sexual season, charactrerized by maximal spermatogenetic and sexual behavior activities in males and in estrus behavior and ovulatory cyclicity in females, generally occurs in autumn and winter. However, males are generally starting and ending earlier their sexual season than females, this advance being more marked in subtropical latitudes (i.e. 3 vs 1 month). This reproductive seasonality causes a seasonal production of milk and meat. Regardless of the latitude of origin of the goats, this seasonality is, in both sexes, mainly synchronized by the annual variations in photoperiod, which induce changes in estradiol and testosterone negative feedbacks on LH secretion, constituting the main neuroendocrine mechanism responsible for reproductive seasonality. Nonethless, the sociosexual interactions between bucks and goats and between bucks themselves can break the natural inhibition of sexual activity during the seasonal sexual rest. Indeed, the introduction of a male into a group of seasonal anestrous goats immediately leads to a resumption of the activity of the hypothalamo-pituitary-gonad axis, allowing females to display estrus and ovulations within few days after joining (Walkden-Brown et al., 1999). This is the "short-term male effect". Recently, we described that the permanent presence of bucks made sexually active by photoperiodic treatments stimulate sexual activity during seasonal anestrus and allows females to ovulate throughout the year (Delgadillo et al., 2015). This is what we called the "long-term male effect". Finally, we recently described that, as in females, the introduction of a sexually active buck into a group of seasonally inactive bucks in sexual rest immediately leads to a resumption of the activity of the hypothalamo-pituitary-gonad axis, improving spermatogenetic and sexual behavior activities of recipient bucks. This is what we called the “buck-to-buck-effect”, or more generally, the “male-to-male effect” (Delgadillo et al., 2022). These three sexual biostimulation techniques to control caprine reproduction in a sustainable way, without the use of exogenous hormones, will be described in the present article

    Conservation laws and Hamilton-Jacobi equations on a junction: the convex case

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    International audienceThe goal of this paper is to study the link between the solution to an Hamilton-Jacobi (HJ) equation and the solution to a Scalar Conservation Law (SCL) on a special network. When the equations are posed on the real axis, it is well known that the space derivative of the solution to the Hamilton-Jacobi equation is the solution to the corresponding scalar conservation law. On networks, the situation is more complicated and we show that this result still holds true in the convex case on a 1:1 junction. The correspondence between solutions to HJ equations and SCL on a 1:1 junction is done showing the convergence of associated numerical schemes. A second direct proof using semi-algebraic functions is also given. Here a 1:1 junction is a simple network composed of two edges and one vertex. In the case of three edges or more, we show that the associated HJ germ is not a L 1-dissipative germ, while it is the case for only two edges. As an important byproduct of our numerical approach, we get a new result on the convergence of numerical schemes for scalar conservation laws on a junction. For a general desired flux condition which is discretized, we show that the numerical solution with the general flux condition converges to the solution of a SCL problem with an effective flux condition at the junction. Up to our knowledge, in previous works the effective condition was directly implemented in the numerical scheme. In general the effective flux condition differs from the desired one, and is its relaxation, which is very natural from the point of view of Hamilton-Jacobi equations. Here for SCL, this effective flux condition is encoded in a germ that we characterize at the junction

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